Dysautonomia, Hypermobility Spectrum Disorders and Mast Cell Activation Syndrome as Migraine Comorbidities.

PURPOSE OF REVIEW: Dysautonomia refers to the dysfunction of the autonomic nervous system and encompasses a wide variety of autonomic symptoms and disorders. The most common autonomic disorders are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be encountered in clinical practice as part of a triad of dysautonomia, hypermobility spectrum disorders (HSD), and mast cell activation syndrome (MCAS). Migraine is one of the most common comorbidities of POTS, HSD, and MCAS; conversely, these conditions are also prevalent in patients with migraine, especially in those with multiple systemic symptoms, such as chronic dizziness, lightheadedness, orthostatic intolerance, joint pain, and allergic symptoms. Diagnostic criteria, pathophysiologic mechanisms, and therapeutic considerations in patients with migraine and comorbid dysautonomia, HSD, and MCAS are reviewed. RECENT FINDINGS: Numerous studies indicate a significant overlap and shared pathophysiology in migraine, dysautonomia, HSD, and MCAS. In clinical setting, dysautonomia, HSD, and MCAS may present a diagnostic and therapeutic challenge in patients with migraine and require a high index of suspicion on the part of the neurologist. Diagnosis and treatment of these complex disorders in patients with migraine is essential to comprehensive patient-centric care, reduced symptom burden, and improved functional impairment secondary to both migraine and comorbidities.

Prospective randomized study comparing permanent pacing with rate drop response and closed loop stimulation in patients with vasovagal syncope where permanent pacing is indicated and selected as the appropriate treatment option.

BACKGROUND: Pacing for vasovagal syncope is established. Two pacing algorithms are available. The rate-drop-response (RDR-Medtronic) is triggered by falling heart rate acting with modified rate-hysteresis. The closed loop stimulation or system (CLS-Biotronik) is triggered by impedance changes in the right ventricle reflecting falling volume and rising contractility. These are very different physiologically. Both algorithms carry favorable reports in clinical use. METHODS: A randomized-controlled superiority trial is proposed to compare the two algorithms for the control of vasovagal syncope in patients for whom pacing is indicated by current guidelines in North America and Europe. Available recent evidence may be seen as supporting superiority of CLS. No comparison between the two algorithms has been made. In this trial, patients will be centrally randomized to one or other algorithm on a 1:1 basis. Two-hundred-seventy-six patients in each group will be recruited. Sample size is determined using a confidence interval of 95%, a power of 90%, and a drop-out rate of 10% to detect an 11% difference between CLS and RDR. Recurrent symptom comparison will be made by an independent committee. The Co-primary endpoints will be recurrent syncope burden compared with that in 24-months preimplant, and occurrence of syncope in 24-months follow-up. Each outcome will be compared between the two algorithms. Secondary endpoints will be program and drug therapy changes over 24-months follow-up and quality of life by questionnaire at baseline,1 and 2 years. RESULTS AND CONCLUSIONS: These are anticipated to clarify the device algorithm choice and, therefore, to improve patient care.

Ganglionated plexi ablation in the right atrium for the treatment of cardioinhibitory syncope.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered 'gateway' of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines.

Demonstrating new-onset or worsened sudomotor function post-COVID-19 on comparative analysis of autonomic function pre-and post-SARS-CoV-2 infection.

Background: Autonomic dysfunction including sudomotor abnormalities have been reported in association with SARS-CoV-2 infection. Objective: There are no previous studies that have compared autonomic function objectively in patients pre- and post- SARS-CoV-2 infection.We aimed to identify if SARS-CoV-2 virus is triggering and/or worsening dysautonomia by comparing autonomic function tests in a group of patients pre-and post-SARS-CoV-2 infection. Design/methods: Six participants were enrolled and divided into two groups. The first group of 4 participants reported worsened autonomic symptoms post-SARS-CoV-2 infection. These individuals had their first autonomic test prior to COVID-19 pandemic outbreak (July 2019-December 2019). Autonomic function testing was repeated in these participants, 6 months to 1-year post-SARS-CoV-2 infection (June 2021).The second group of 2 participants reported new-onset autonomic symptoms post-COVID-19 infection and were also tested within 6 months post-SARS-CoV-2 infection.All participants had mild COVID-19 infection per WHO criteria. They had no evidence of large fiber neuropathy as demonstrated by normal neurophysiological studies (EMG/NCS). They were all screened for known causes of autonomic dysfunction and without risk factors of hypertension/hyperlipidemia, thyroid dysfunction, diabetes/prediabetes, vitamin deficiencies, history of HIV, hepatitis, or syphilis, prior radiation or chemical exposure or evidence of monoclonal gammopathy, or autoimmune condition. Results: Participants were female (age: 21-37y) and all endorsed orthostatic intolerance (6/6). Gastrointestinal symptoms (⅚), new-onset paresthesias, (3/6), and sexual dysfunction (2/6) were reported. Parasympathetic autonomic function remained stable 6-months to 1-year post-COVID-19 infection and no parasympathetic dysfunction was demonstrated in participants with new-onset dysautonomia symptoms. Postural orthostatic tachycardia was noted in half of the patients, being observed in one patient pre- SARS-CoV-2 infection and persisting post-SARS-CoV-2 infection; while new-onset postural tachycardia was observed in 1/3rd of patients. Sympathetic cholinergic (sudomotor) dysfunction was demonstrated in ALL participants. Worsened, or new-onset, sudomotor dysfunction was demonstrated in those with mild or normal sudomotor function on pre-COVID-19 autonomic testing. Conclusions: Sympathetic adrenergic and cholinergic dysautonomia probably account for some of the symptoms of Long COVID-19. Sudomotor dysfunction was demonstrated as consistently worsened or new-sequelae to COVID-19 infection. COVID-19 may be responsible for triggering new-onset or worsened small-fiber neuropathy in this sample, supporting previously reported studies with similar findings. However, the findings in our study are preliminary, and studies with larger sample size are needed to confirm these observations.

Vasovagal Syncope during Office Hysteroscopy-A Frequently Overlooked Unpleasant Complication.

Due to technological advancements in miniaturization of instruments and improved optics, the number of office hysteroscopic procedures has increased over time. Office hysteroscopy is preferred due to avoidance of general anesthesia and decreased overall cost. Vasovagal syncope has been implied as the most common complication. Vasovagal syncope is associated with inappropriate reflex vasodilation and bradycardia in the setting of an acute malfunction between the autonomic nervous system and the cardiovascular system; however, there is no mortality associated with vasovagal syncope. A management strategy for acute vasovagal reflex during office hysteroscopy is proposed in order to manage this common complication.

Improved health-related quality of life after cardioneuroablation in patients with vasovagal syncope.

BACKGROUND: As the most common cause of syncope, vasovagal syncope (VVS) is mediated by parasympathetic overactivity and/or sympathetic withdrawal. Although catheter ablation of ganglionated plexi or cardioneuroablation has been used to treat VVS, its role in quality of life (QoL) has not been formally evaluated. The aim of this study was to demonstrate if this novel treatment results in improvement QoL of patients with VVS. METHODS: Twenty-seven consecutive patients (age: 34 ± 14 years, 51.8% male) with dominant cardioinhibitory type VVS were prospectively enrolled in the study. After confirmation of > 3 s asystole on head-up tilt testing (HUT), all patients underwent cardioneuroablation. ECGs were obtained prior to procedure and at 12-month follow-up visit. HUTs were repeated 1 month after cardioneuroablation procedures. QoL was assessed with the use of SF-36, EQ-5D, and EQ VAS questionnaires. RESULTS: ECG, HUT, and QoL data were available in all patients. At 12-month follow-up, heart rate on rest ECG significantly increased (from 74 ± 15 to 84 ± 14 bpm, p = 0.003). Repeated HUTs were negative in 23 (85.1%) patients. All of 27 patients remained free of syncope. QoL assessed by SF-36 score significantly improved in postprocedural follow-up (92 ± 9 and 96 ± 11, p = 0.016). Similarly, significant improvements in mobility, self-care, and usual activity domains of EQ-5D were observed (mean scores of 3.0 ± 1.5 and 2.1 ± 1.3, p < 0.001; 1.3 ± 0.9 and 1.2 ± 0.6, p = 0.041; 1.7 ± 1.0 and 1.4 ± 0.8 respectively). EQ-VAS score also improved significantly (39 ± 24 to 77 ± 18, p < 0.001). CONCLUSION: Our findings suggest that cardioneuroablation may be associated with intermediate term improvement in QoL in patients with VVS.

Prospective Evaluation of Autonomic Dysfunction in Post-Acute Sequela of COVID-19.

BACKGROUND: Patients with post-acute sequela of COVID-19 (PASC) often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link postural orthostatic tachycardia syndrome (POTS) to PASC. No prospective analysis has been performed. OBJECTIVES: This study performed head-up tilt table (HUTT) testing in symptomatic patients with PASC to evaluate for orthostatic intolerance suggestive of autonomic dysfunction. METHODS: We performed a prospective, observational evaluation of patients with PASC complaining of poor exertional tolerance, tachycardia with minimal activity or positional change, and palpitations. Exclusion criteria included pregnancy, pre-PASC autonomic dysfunction or syncope, or another potential explanation of PASC symptoms. All subjects underwent HUTT. RESULTS: Twenty-four patients with the described PASC symptoms were included. HUTT was performed a mean of 5.8 ± 3.5 months after symptom onset. Twenty-three of the 24 had orthostatic intolerance on HUTT, with 4 demonstrating POTS, 15 provoked orthostatic intolerance (POI) after nitroglycerin, 3 neurocardiogenic syncope, and 1 orthostatic hypotension. Compared with those with POTS, patients with POI described significantly earlier improvement of symptoms. CONCLUSIONS: This prospective evaluation of HUTT in patients with PASC revealed orthostatic intolerance on HUTT suggestive of autonomic dysfunction in nearly all subjects. Those with POI may be further along the path of clinical recovery than those demonstrating POTS.

The impact of atrial mechanical function on age-dependent presentation of neurocardiogenic syncope.

BACKGROUND: The contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive. HYPOTHESIS: We assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences. METHODS: We assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age <35 (group A, n = 56) and >35 years (group B, n = 68). Echocardiographic indices were measured before head-up tilt test (HUTT). RESULTS: A total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2 , p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p < .001) and LA peak strain rate (reservoir phase 1.83 ± 1.04 vs. 1.36 ± 0.96 1/s, p = .012, conduit phase 2.36 ± 1.25 vs. 1.36 ± 0.78 1/s, p = .001). Group A showed smaller minimum right atrial (RA) volume, better RA systolic function, superior left ventricular diastolic indices, and lower filling pressures. Group A patients were more likely to have >3 recurrences (82.0% vs. 50.1%, p < .05). CONCLUSIONS: Patients with younger age of NCS onset and more syncopal recurrences manifest smaller LA and RA dimensions with distinct patterns of systolic and diastolic function and better LA reservoir and contraction properties. These findings may indicate an increased susceptibility to preload reduction, thereby triggering the NCS mechanism.

Further Observations on the Use of Pacemakers in Patients with Postural Orthostatic Tachycardia Syndrome with Demonstrated Asystole.

A subgroup of postural orthostatic tachycardia syndrome (POTS) patients may also have features of neurocardiogenic syncope (NCS). Syncope and presyncope are predominant clinical features in this subgroup of patients. Asystole has been reported as the cause of some recurrent syncopal episodes following evaluation with an implantable loop recorder (ILR). We present our experience of pacing in a group of patients with POTS and NCS, which resulted in the complete elimination of syncope. We reviewed the charts of 500 patients at the University of Toledo Medical Center from 2003 to 2013 and identified 40 patients who were eligible for inclusion in this study. Patients were included in this study if they had clinical features of POTS and unusually frequent episodes of syncope. All study participants subsequently underwent ILR implantation. Forty patients, including 32 (80%) women, aged 33 ± 13 years were included in this study. All patients demonstrated prolonged asystole (> 6 seconds) or severe bradycardia (heart rate < 30 bpm) during their syncope. Ten patients demonstrated an asystole of more than 10 seconds and also had prolonged and convulsive syncope. All patients had abrupt syncope without any warning signs. All 40 patients underwent dual-chamber pacemaker implantation. Syncope was eliminated in all 40 patients following pacemaker implantation; however, they continued to experience orthostatic tachycardia. Our findings support that dual-chamber pacing may help to eliminate syncope in a subgroup of POTS patients with recurrent syncope and prolonged asystole on ILR.

Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients.

OBJECTIVE: To describe clinical features, diagnostic findings, treatments, and outcomes in patients with new-onset postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders following SARS-CoV-2 infection (COVID-19). METHODS: We retrospectively reviewed medical records for patients who presented with persistent neurologic and cardiovascular complaints between April and December 2020 following COVID-19 infection. RESULTS: Twenty patients (70% female) were included in this study.Fifteen had POTS, 3 had neurocardiogenic syncope, and 2 had orthostatic hypotension. Six patients had abnormalities on cardiac or pulmonary testing, and 4 had elevated autoimmune or inflammatory markers. All patients were treated with non-pharmacologic therapies, and most required pharmacologic therapies. Six to 8 months after COVID-19, 17 (85%) patients had residual autonomic symptoms, with 12 (60%) unable to return to work. CONCLUSIONS: POTS can follow COVID-19 in previously healthy patients. Appropriate diagnostic investigations and therapies are necessary to identify and treat autonomic dysfunction after COVID-19.

Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study.

BACKGROUND: A Postural orthostatic tachycardia syndrome (POTS) is infrequently diagnosed in routine practice because of the variable range of symptoms that could be seen in cardiac rhythm disorders, vertigo, chronic fatigue syndrome and anxiety panic disorder. POTS is a chronic debilitating condition that affects day to day efficient working of an individual. We have planned a study to look for POTS in patients who are having orthostatic intolerance symptoms and underwent a head-up tilt table test (HUTT). AIM: To study the prevalence of POTS in patients of orthostatic intolerance (OI) symptoms and to analyze symptomatology, its association with neurocardiogenic syncope (NCS), and its outcome. METHODS: We reviewed the medical records of 246 patients presented with symptoms of OI seen at our centre from January 2010 till March 2019. Out of them, 40 patients included, those qualifying the criteria for POTS on HUTT. RESULTS: The mean age of the cohort was 25.90 ± 10.33 years with a range of 15 to 55 years, and males comprised 52.5% (21/40) of total patients. The most frequent presenting orthostatic symptoms of POTS patients are loss of consciousness (77.5%), lightheadedness (75%), and palpitation (67.5%). A total of 18 patients (45%) had coexisting neurocardiogenic syncope. CONCLUSION: POTS is a prevalent condition and have a significant impact on the quality of life, and the majority of patients may not present with OI symptoms during HUTT. We have to keep this possibility in young patients of transient loss of consciousness because it may coexist with NCS.

Catheter ablation of right atrial ganglionated plexi to treat cardioinhibitory neurocardiogenic syncope: a long-term follow-up prospective study.

PURPOSE: Several reports have focused on biatrial ganglionated plexi (GP) transcatheter ablation to treat cardioinhibitory neurocardiogenic syncope (CNS). Considering that anatomical studies showed a significant number of GP in the right atrium (RA), we hypothesized that RA "cardioneuroablation" could be an effective treatment for CNS. METHODS: Eighteen consecutive patients (mean age: 36.9 ± 11.2 years) with severe CNS were submitted to transcatheter ablation of GPs in the RA alone using an anatomical approach. Head up tilt test evaluation was performed during the follow-up period at 6, 12, and 24 months and in case of significant symptoms, while heart rate variability parameters were evaluated at patients discharge at 1, 3, 6, 12, 24, and 36 months after ablation. RESULTS: At a mean follow-up of 34.1 ± 6.1 months, 3 (16.6%) patients experienced syncopal episodes and 5 patients (27.7%) only prodromal episodes. Syncopal and prodromal recurrences were significantly decreased both in overall population (P = 0.001) and in symptomatic patients after ablation (P = 0.003). Heart rate variability analysis showed the loss of autonomic balance secondary to a reincrease of sympathetic tone after the acute phase faster than vagal tone more evident at 12 months (LF/HF vs preablation, P < 0.001) and persistent until 24 months. Finally, a good correlation was observed between symptomatic events and the extension of RF lesions in supero-, middle-, and infero-posterior RA areas (r = 0.73, P = 0.03; r = 0.85, P = 0.02; r = 0.87, P = 0.004, respectively). CONCLUSIONS: Cardioneuroablation in the RA can be considered safe and an effective technique to treat CNS episodes.

Abordaje del síncope situacional en Atención Primaria. De la sospecha al diagnóstico / Approach to situational syncope in Primary Care. From the suspicion to the diagnosis

Se presenta el caso de un adolescente de 12 años con episodios repetidos de sensación de pérdida de conciencia inminente con recuperación posterior completa, mientras se prepara para ir al colegio. La anamnesis, exploración y pruebas complementarias serán clave para realizar el diagnóstico de exclusión y la posterior pauta de normas de conducta para su evitación (AU)

We report the case of a 12-year-old male patient with repeated episodes of sudden and transient loss of consciousness sensation with immediate recovery, while preparing himself for school. Anamnesis, exploration and complementary tests will be key elements for a diagnosis of exclusion and the subsequent set of guidelines for its avoidance (AU)

Impaired consciousness when scuba diving associated with vasovagal syncope.

INTRODUCTION: Drowning is likely to result from impairment of consciousness when scuba diving. Causes include toxic effects of breathing gas, including nitrogen narcosis and oxygen toxicity, and arterial gas embolism. METHODS: Review of the medical records of scuba divers who had impaired consciousness underwater that could not be attributed to toxic effects of breathing gas or arterial gas embolism. RESULTS: Four scuba divers had episodes of impaired consciousness when at shallow depths (8-18 m) underwater. The descriptions of the episodes were very similar. Three had histories of recurrent episodes of vasovagal syncope on land. CONLCUSIONS: Absence of other causes for their impaired consciousness underwater leads to the conclusion that the probable cause was vasovagal syncope.

Impact of Yoga on Cardiac Autonomic Function and Arrhythmias.

With the expanding integration of complementary and alternative medicine (CAM) practices in conjunction with modern medicine, yoga has quickly risen to being one of the most common CAM practices across the world. Despite widespread use of yoga, limited studies are available, particularly in the setting of dysrhythmia. Preliminary studies demonstrate promising results from integration of yoga as an adjunct to medical therapy for management of dysrhythmias. In this review, we discuss the role of autonomic nervous system in cardiac arrhythmia,interaction of yoga with autonomic tone and its subsequent impact on these disease states. The role of yoga in specific disease states, and potential future direction for studies assessing the role of yoga in dysrhythmia.

Usefulness of post-procedural heart rate response to predict syncope recurrence or positive head up tilt table testing after cardioneuroablation.

AIMS: Previous reports have suggested that cardioneuroablation (CNA) can be effective in reducing syncopal recurrences in patients with vasovagal syncope (VVS). This study assessed the efficacy of CNA in preventing a positive response to head-up tilt testing (HUT). METHODS AND RESULTS: This is a single-centre retrospective study reviewing prospectively collected data. Fifty-one consecutive patients with VVS were included in the study. After confirmation of >3 s asystole on HUT, all patients underwent CNA. Head-up tilt testing was repeated 1 month after CNA. The main outcome measures were recurrence of syncope episode and positive response on HUT. During a median follow-up period of 11 months (interquartile range 3-27 months), all but 3 (5.8%) of 51 patients were free of syncope. Repeated HUTs were negative in 44 (86.2%) patients. When patients with recurrent syncope were excluded, vasodepressor response was seen in three cases and cardioinhibitory response in one case, respectively. Cardioneuroablation caused significant and durable shortening of RR interval in all cases. This effect was significantly higher in patients without positive HUT responses. CONCLUSION: This pilot study shows that CNA can effectively prevent recurrent syncopal episodes in patients with refractory VVS. Head-up tilt testing seems as a valuable diagnostic tool not only to select suitable candidates and but also to evaluate success of CNA.

Utility of Head up Tilt Table Testing to Demonstrate Selective Denervation of the Sinus Node after Cardioneuroablation.

A 65-year-old female who underwent cardioneuroablation for recurrent vasovagal syncope presented for 6 month follow-up visit. She had no further syncope after the procedure. A follow up tilt table testing (TT) demonstrated sinus tachycardia and variable degrees of atrioventricular block (AVB) after sublingual glyceryl trinitrate. She had no syncope during the test. As per existing knowledge, the occurrence of AVB during vasovagal reaction induced by TT should be preceded by sinus rhythm slowing.  In this patient, sinus tachycardia during TT demonstrates highly specific denervation of ganglion cells which send postganglionic fibers directly to the sinus node without obvious influence on the atrioventricular node.

The Repolarization Period during the Head-Up Tilt Test in Children with Vasovagal Syncope.

BACKGROUND: Electrocardiography (ECG) and the head-up tilt test (HUTT) are vital in clinical work-up in children with vasovagal syncope (VVS). Ventricular repolarization parameters (QT) measured during the HUTT can be indicative of electrical instability; however, these parameters are not frequently assessed. This study aimed to investigate if ventricular repolarization parameters measured during the HUTT could be indicative of future ventricular arrhythmias in children with syncope. METHODS: The shape and amplitude of the T-wave and parameters of the repolarization period (QT, QTpeak, Tpeak-Tend) were evaluated in a resting ECG performed on the first day of hospitalization and in ECGs performed during three phases of the HUTT. RESULTS: In the after-tilt phase of the HUTT, 19/30 children displayed a change in T-wave morphology. QTc was significantly longer in VVS I compared to that in VVS II patients, but not in the controls (p = 0.092). CONCLUSIONS: We need further follow-up studies to establish the clinical importance of abnormal dynamics of the repolarization period in children with VVS and negative HUTT. Therefore, children with abnormal T-wave refraction and prolonged duration of the TpTe should remain under the care of a cardiological outpatient.