Postural Syncope Research Articles

A phase 2 safety and efficacy study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma.

9510 Background: Darovasertib is a protein kinase C (PKC) inhibitor with meaningful activity in metastatic uveal melanoma (UM) due to its effect on PKC delta downstream of canonical GNAQ/GNA11 mutations. To date, its clinical activity in patients with localized primary disease has not been assessed in either neoadjuvant or adjuvant settings. Methods: Patients planned for enucleation with localized UM were treated in an initial safety cohort with darovasertib 300mg BID for 1 month (n=3 patients), and then following DSMB agreement in an expansion cohort for up to 6 months (n=12 patients) as neoadjuvant treatment prior to definitive management (enucleation, plaque brachytherapy or EBRT) across 3 Australian centers. All patients were eligible to receive up to 6 months of adjuvant treatment with darovasertib at investigator discretion after definitive management of their primary tumour. Tumour volume was calculated by the rotational ellipsoid method. Results: 15 patients (male n=7, female n=8; median age 62 years (range, 33-76 years)) were enrolled. At baseline, AJCC tumor stages were T3a (n=5), T3b (n=4), T4a (n=4), T4b (n=2), and the median tumor size (maximum thickness/diameter/volume) was 9.7mm/ 15.6 mm/ 2463 mm3. At datalock; 11/15 patients had completed primary treatment, 4/15 remained on neoadjuvant treatment, 6 patients received adjuvant darovasertib after primary treatment of their UM with 3 patients completing the planned 6-months . Median tumor shrinkage (maximum height/base/volume change) was 11.2%/ 7.6%/ 22.7% after 1 month of treatment and 31.7%/ 11.9% /45.3% after 6 months. At datalock, 6/9 (66%) currently completed neoadjuvant patients were converted to plaque brachytherapy (n=5) or EBRT (n=1) with 3 ongoing. One patient with high-risk cytogenetic features had relapsed with metastatic disease despite receiving 6-months of neoadjuvant darovasertib and another 6-months of adjuvant treatment. Treatment emergent adverse events included postural hypotension (Gr1/2 – 13/13%), syncope (Gr3 – 13%), rash (Gr1/2 – 33/5%), pruritis (Grr1 – 13%), dizziness (Gr1 – 27%), fatigue (Gr1/2 – 30/5%), nausea (Gr1/2 – 73/6%), vomiting (Gr1 – 40%), and diarrhea (Gr1 – 60%). Updated results, histopathological and genomic outcomes will be presented. Conclusions: NADOM provides the first evidence that a globe-salvage neoadjuvant treatment strategy in UM is feasible, safe, and efficacious. The results suggest that PKC inhibition with darovasertib can induce clinically meaningful tumor shrinkage in patients with primary UM patients who otherwise require enucleation. Larger trials are in now progress (NCT05907954) to further quantify visual and oncological outcomes. Clinical trial information: 05187884.

A Method to Assess Granger Causality, Isolation and Autonomy in the Time and Frequency Domains: Theory and Application to Cerebrovascular Variability.

Concepts of Granger causality (GC) and Granger autonomy (GA) are central to assess the dynamics of coupled physiologic processes. While causality measures have been already proposed and applied in time and frequency domains, measures quantifying self-dependencies are still limited to the time-domain formulation and lack of clear spectral representation. We embed into the linear parametric framework for computing GC from a driver X to a target process Y a measure of Granger Isolation (GI) quantifying the part of the dynamics of Y not originating from X, and a new spectral measure of GA assessing frequency-specific patterns of self-dependencies in Y. The measures are illustrated in theoretical simulations and applied to time series of arterial pressure and cerebral blood flow obtained in syncope subjects and healthy controls. Simulations show that GI is complementary to GC but not trivially related to it, while GA reflects the regularity of the internal dynamics of the target process. In the application to cerebrovascular interactions, spectral GA quantified the physiological response to postural stress of slow cerebral blood flow oscillations, while spectral GC and GI detected an altered response to orthostasis in syncope subjects, likely related to impaired cerebral autoregulation. The new spectral measures of GI and GA are useful complements to GC for the analysis of interacting oscillatory processes, and detect pathophysiological responses to postural stress which cannot be traced in the time domain. The thorough assessment of causality, isolation and autonomy opens new perspectives for the analysis of coupled processes in both physiological and clinical investigations.

Modern methods of researching autonomic functions in children with syncope: A literature review

The research of autonomic functions in children with non-cardiogenic syncope allows improving differential diagnosis and treatment tactics in children depending on the pathogenetic mechanisms of syncope development. The purpose of the research was to analyse modern scientific achievements in the field of autonomic functions in children with different types of syncope. The review used the full texts of English-language studies published between January 2018 and December 2022 and published in the PubMed Medline and Scopus databases. It has been established that the active orthostasis test, tilt test, circadian blood pressure rhythms and heart rate variability are the most commonly used functional autonomic tests in paediatric practice. They allow evaluating the spectrum of pathological cardiovascular reactions in a standing position; identifying types of orthostatic hypotension and causes of orthostatic intolerance; diagnosing orthostatic hypertension, postural orthostatic tachycardia syndrome, presyncope or syncope; to differentiating between sympathetic and parasympathetic autonomic dysfunctions and psychogenic transient syncope and epilepsy; to recommend orthostatic training as a method of treatment of syncope with an orthostatic mechanism of development. Despite this, there is no consensus on the definition of autonomic disorders and the methodology for conducting functional autonomic tests in children of different ages, considering their gender, body mass index and time of assessment during the day. Thus, functional autonomic tests are additional methods of physical and instrumental examination of the patient that allow effective assessment of the autonomic nervous system and possible mechanisms of syncope development, differentiation of transient loss of consciousness, stratification of future risks and optimisation of treatment and preventive tactics of the child's management based on an individual patient-centred approach

Concomitant evaluation of cardiovascular and cerebrovascular controls via Geweke spectral causality to assess the propensity to postural syncope

The evaluation of propensity to postural syncope necessitates the concomitant characterization of the cardiovascular and cerebrovascular controls and a method capable of disentangling closed loop relationships and decomposing causal links in the frequency domain. We applied Geweke spectral causality (GSC) to assess cardiovascular control from heart period and systolic arterial pressure variability and cerebrovascular regulation from mean arterial pressure and mean cerebral blood velocity variability in 13 control subjects and 13 individuals prone to develop orthostatic syncope. Analysis was made at rest in supine position and during head-up tilt at 60°, well before observing presyncope signs. Two different linear model structures were compared, namely bivariate autoregressive and bivariate dynamic adjustment classes. We found that (i) GSC markers did not depend on the model structure; (ii) the concomitant assessment of cardiovascular and cerebrovascular controls was useful for a deeper comprehension of postural disturbances; (iii) orthostatic syncope appeared to be favored by the loss of a coordinated behavior between the baroreflex feedback and mechanical feedforward pathway in the frequency band typical of the baroreflex functioning during the postural challenge, and by a weak cerebral autoregulation as revealed by the increased strength of the pressure-to-flow link in the respiratory band. GSC applied to spontaneous cardiovascular and cerebrovascular oscillations is a promising tool for describing and monitoring disturbances associated with posture modification.Graphical

The Implementation of Renal Denervation in the Management of Resistant Hypertension Despite Use of Multitherapy Antihypertensives at Maximally Tolerated Doses: A Contemporary Literature Review.

Refractory hypertension is highly prevalent among the hypertensive population, and current clinical management has failed to provide optimal control for these individuals. This subtype of arterial hypertension is defined as a persistently elevated systolic blood pressure reading of 140 mmHg, or higher, despite multiple antihypertensive use at maximally tolerated dosing. These patients have an elevated risk of cardiovascular and renal complications, urging for the need of more effective therapeutic management. Renal sympathetic efferent nerves have been noted to play an important role in volume and blood pressure homeostasis. Before the implementation of oral antihypertensives, the use of surgical lumbar sympathectomy for the reduction of persistent hypertension was considered a life-saving approach. However, individuals were left with debilitating side effects, such as postural hypotension, syncope, and impotence. A new and minimally invasive technique has been proposed, where the kidneys undergo selective denervation in hopes of providing decreased cardiovascular morbidity and mortality for patients with resistant hypertension. Some studies demonstrated promising outcomes with a reduction in blood pressure, a decrease in medication reliance, and a potential long-lasting effect of the procedure with an overall improvement in cardiovascular health. Unfortunately, most of the available data was obtained from observational, uncontrolled studies with short-term follow-up, small sample sizes, and high variability in blood pressure measurement. Therefore, further evidence is needed to determine whether renal denervation provides long-term benefits for blood pressure control and improves outcomes for mortality and cardiovascular events in this patient population.

CARDIOVASCULAR AUTONOMIC DYSFUNCTION IN HIV-POSITIVE PATIENTS AND ITS CORRELATION WITH CD4 CELL COUNT

According to Global human immunodeciency virus and acquired immunodeciency disease syndrome statistics, 38.4 million(33.9 million-43.8 million) people live globally with HIV in 2021, and 1.5 million people became newly infected with HIV in 2021(1). As per India HIV estimation report 2020, national adult (15–49 years) HIV prevalence was estimated at 0.22% (0.17%–0.29%) in 2020, 0.23% (0.18%–0.31%) among males and 0.20% (0.15%– 0.26%) among females(2). HIV is a condition which can progressively affect almost all body organs and systems due to immune system failure. Infection with HIV is well known to cause peripheral neuropathy and other neurological complication thus affecting the quality of life(3). Autonomic nervous system involvement can affect heart rate, vasomotor tone, sexual function, gastrointestinal motility, urination, thermoregulation and production of tears and saliva. This can lead to diverse symptoms like postural syncope, impotence, sweating, diarrhea/constipation, dry eyes and mouth, urinary incontinence and changes in skin temperature. Abnormalities in cardiac autonomic function occur at all CD4 levels(4,5). The aim of our study is to assess autonomic dysfunction in HIV-positive patients and to show the correlation between decreasing CD4 + T cell counts with increasing severity of disease in the form of autonomic dysfunction.

A 29-year-old woman with recurrent syncope.

A 29-year-old woman presented to the internal medicine clinic with 2 months of postural syncope. Blood pressure as measured in her upper arm was 79/49 mm Hg and her heart rate was 90 beats/min, with no postural changes. Investigations (including electrocardiography, routine bloodwork and adrenal

Spectral decomposition of cerebrovascular and cardiovascular interactions in patients prone to postural syncope and healthy controls

We present a framework for the linear parametric analysis of pairwise interactions in bivariate time series in the time and frequency domains, which allows the evaluation of total, causal and instantaneous interactions and connects time- and frequency-domain measures. The framework is applied to physiological time series to investigate the cerebrovascular regulation from the variability of mean cerebral blood flow velocity (CBFV) and mean arterial pressure (MAP), and the cardiovascular regulation from the variability of heart period (HP) and systolic arterial pressure (SAP). We analyze time series acquired at rest and during the early and late phase of head-up tilt in subjects developing orthostatic syncope in response to prolonged postural stress, and in healthy controls. The spectral measures of total, causal and instantaneous coupling between HP and SAP, and between MAP and CBFV, are averaged in the low-frequency band of the spectrum to focus on specific rhythms, and over all frequencies to get time-domain measures. The analysis of cardiovascular interactions indicates that postural stress induces baroreflex involvement, and its prolongation induces baroreflex dysregulation in syncope subjects. The analysis of cerebrovascular interactions indicates that the postural stress enhances the total coupling between MAP and CBFV, and challenges cerebral autoregulation in syncope subjects, while the strong sympathetic activation elicited by prolonged postural stress in healthy controls may determine an increased coupling from CBFV to MAP during late tilt. These results document that the combination of time-domain and spectral measures allows us to obtain an integrated view of cardiovascular and cerebrovascular regulation in healthy and diseased subjects.

Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases.

The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0–50.0) mg/day vs. 25.0 (25.0–50.0) mg/day, p < 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p < 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05–1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol.

Dynamic cerebrovascular autoregulation in patients prone to postural syncope: Comparison of techniques assessing the autoregulation index from spontaneous variability series.

Three approaches to the assessment of cerebrovascular autoregulation (CA) via the computation of the autoregulation index (ARI) from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) were applied: 1) a time domain method (TDM); 2) a nonparametric method (nonPM); 3) a parametric method (PM). Performances were tested over matched and surrogate unmatched pairs. Data were analyzed at supine resting (REST) and during the early phase of 60° head-up tilt (TILT) in 13 subjects with previous history of postural syncope (SYNC, age: 28±9yrs.; 5 males) and 13 control individuals (noSYNC, age: 27±8yrs.; 5 males). Analysis was completed by computing autonomic markers from heart period (HP) and systolic arterial pressure (SAP) variability series via spectral approach. HP and SAP spectral indexes suggested that noSYNC and SYNC groups exhibited different autonomic responses to TILT. ARI analysis indicated that: i) all methods have a sufficient statistical power to separate matched from unmatched pairs with the exception of nonPM applied to impulse response; ii) ARI estimates derived from different methods might be uncorrelated and, even when correlated, might exhibit a significant bias; iii) orthostatic stressor did not induce any evident ARI change in either noSYNC or SYNC individuals; iv) this conclusion held regardless of the method. Methods for the ARI estimation from spontaneous variability provide different ARIs but none indicate that noSYNC and SYNC subjects have different dynamic component of CA.

Abstract 11329: Prospective Analysis of Vascular Resistance in Patients with Persistent Tachycardia and or Dyspnea on Exertion in the Post Acute Sequela of Covid-19 Syndrome

Introduction: The cause of tachycardia and dyspnea on exertion (DOE) in the Post Acute Sequelae CoV-2 syndrome (PASC) has yet to be identified. While endothelial invasion of the virus is well documented, how that might explain PASC is unknown. Hypothesis: Covid induced changes in vascular signaling to autonomic regulatory centers can induce sinus tachycardia and DOE. Methods: In a prospective, observational study, we enrolled 18 PASC patients who reported DOE or inappropriate tachycardia. All patients had normal left ventricular function, CXR, Hgb and thyroid studies. None had preexisting autonomic dysfunction. Vascular resistance was assessed by echocardiographic measurement of aortic-vascular impedance (Zva)=(systolic BP + mean Ao valve gradient)/stroke volume index. Ambulatory heart rate monitoring and head-up tilt table testing (HUTT) were performed. Results: Consecutively enrolled patients (18) were studied (17 females, ages 27 to 64). None had a significant aortic valve gradient. Zva was elevated in 17 of 18 patients. Ambulatory monitoring revealed episodes of symptomatic sinus tachycardia. Higher average daily heart rates correlated significantly with higher Zva levels (fig1). The 14 patients with DOE trended to higher average Zva levels than the 4 patients without dyspnea (4.13 +- 0.85 vs 3.5 +- 0.24, P=0.14). Of the 17 patients who had HUTT, 16 demonstrated patterns of orthostatic intolerance consistent with excess sympathetic tone including both postural orthostatic tachycardia and neurogenic cardiac syncope. Conclusions: PASC associated sinus tachycardia and HUTT abnormalities result from excess sympathetic tone. Covid-19 vascular injury as evidenced by abnormal Zva values may result in abnormal vascular signaling to autonomic regulatory centers. Resultant increases in sympathetic output may produce inappropriate sinus tachycardia, vasomotor dysregulation and DOE via peripheral vasoconstriction.

Older Age, Polypharmacy, and Low Systolic Blood Pressure Are Associated With More Hypotension-Related Adverse Events in Patients With Type 2 Diabetes Treated With Antihypertensives.

Background and Aims: Low systolic blood pressure (SBP) levels while being treated with antihypertensives may cause hypotension-related adverse events (hrAEs), especially in the elderly, women, and frail patients. We aimed to assess the association between the occurrence of hrAEs and low SBP levels, age, sex, and polypharmacy among patients with type 2 diabetes (T2D) treated with antihypertensives. Methods: In this cohort study, we used the Groningen Initiative to ANalyse Type 2 diabetes Treatment (GIANTT) database which includes patients managed for T2D in primary care from the north of the Netherlands. Patients treated with ≥1 antihypertensive drug and ≥1 SBP measurement between 2012 and 2014 were included. The outcome was the presence of an hrAE, i.e. postural hypotension, dizziness, weakness/tiredness, and syncope in 90 days before or after the lowest recorded SBP level. Age (≥70 vs. <70 years), sex (women vs. men), polypharmacy (5–9 drugs or ≥10 drugs vs. <5 drugs), and SBP level (<130 or ≥130 mmHg) were included as determinants. Logistic regression analyses were conducted for age, sex and polypharmacy, including the SBP level and their interaction, adjusted for confounders. Odds ratios (OR) with 95% confidence intervals (CI) are presented. Results: We included 21,119 patients, 49% of which were ≥70 years old, 52% were women, 57% had polypharmacy, 61% had an SBP level <130 mmHg and 5.4% experienced an hrAE. Patients with an SBP level <130 mmHg had a significantly higher occurrence of hrAEs than patients with a higher SBP level (6.2 vs. 4.0%; ORs 1.41, 95%CI 1.14–1.75, 1.43, 95%CI 1.17–1.76 and 1.33, 95%CI 1.06–1.67 by age, sex, and polypharmacy, respectively). Older patients (OR 1.29, 95%CI 1.02–1.64) and patients with polypharmacy (OR 5–9 drugs 1.27, 95%CI 1.00–1.62; OR ≥10 drugs 2.37, 95% CI 1.67–3.37) were more likely to experience an hrAE. The association with sex and the interactions between the determinants and SBP level were not significant. Conclusion: Low SBP levels in patients with T2D treated with antihypertensives is associated with an increase in hrAEs. Older patients and those with polypharmacy are particularly at risk of hrAEs. Age, sex, and polypharmacy did not modify the risk of hrAEs associated with a low SBP level.

Abstract P223: Vitamin D Supplementation Improves Measures Of Arterial Stiffness And Vascular Function In Adolescents Suffering From Orthostatic Intolerance

Background: In previous work we identified a group of adolescents with orthostatic intolerance (OI) presenting as postural orthostatic tachycardia syndrome or syncope with impairment in autonomic and vascular response upon head up tilt. Low vitamin D level correlated with the severity of symptoms. In this pilot study we hypothesized that vitamin D supplementation will improve the vascular function in these adolescents. Methods: A cohort of twenty Adolescents (mean age= 16.2 years, 4 males) who are vitamin D deficient had a non-invasive measurements of brachial BP, aortic BP, augmentation index at heart rate of 75 beats per minute (AIx75), and carotid-femoral pulse wave velocity (cf-PWV) using the SphygmoCor XCEL System at baseline and after two months of vitamin D supplementation (2000-5000 IU daily based on baseline level). Both right and left side ankle pressure and ankle brachial index (ABI) were assessed using COLIN VP-1000 vascular profiling system. Impedance Cardiography (ICG) was used to estimate total arterial compliance (TAC) and thoracic fluid content (TFC) in supine position at rest and after hand grip challenge. Results: As shown in the table. Compared to baseline, vitamin D supplementation increased vitamin D level, increased TAC and TFC at baseline and under stress challenge. It also tended to reduced AIx75 and cf-PWV and reduced both right and left ankle pressure and ABI Conclusions: Vitamin D supplementation improved different measures of vascular function in adolescent. These data provides evidence of potential therapeutic benefit of vitamin D supplementation for patients suffering from orthostatic intolerance who are vitamin D deficient.

Syncope: A Brief Review

Syncope can be described as the transient loss of consciousness due to decreased blood flow to the brain, also termed as pass out. Syncope may results from a sudden drop in blood pressure, reduced heart rate (bradycardia) or due to fluctuations in the blood volume. People are likely to become conscious and alert immediately after an episode of syncope or pass out but with little confusion. Depending on the etiology, syncope can be categorized into Vasovagal syncope (cardio-neuriogenic syncope), Situational syncope, Postural syncope, Neurological syncope and Metabolic syncope. Syncope and non-syncopal conditions, with real or apparent loss of consciousness, are often differentiated in most cases with an in depth clinical history, but this might sometimes be extremely difficult. In order to develop an effective mechanism?specific treatment, determining the mechanism of syncope is a prerequisite for advising the patients with regard to prognosis.

O-AD003. Postural Orthostatic Tachycardia Syndrome (POTS): A case series from India

Introduction . POTS (Postural Orthostatic Tachycardia Syndrome) is defined as the presence of chronic symptoms of orthostatic intolerance (≥6 months) accompanied by an increased heart rate (HR) ≥30 bpm within 10 minutes of assuming an upright posture in the absence of orthostatic hypotension. It is diagnosed by tilt table testing where the heart rate at base line and on standing is recorded. The incidence and presenting complaints of this disease has not been studied in the Indian subcontinent. Methods . This is a retrospective study where we looked into the data of patients with diagnosis of POTS over a period of 3 years (August 2014–August 2017). We are describing the baseline demographics, clinical presentations, investigations, treatment and follow up of these patients. POTS was diagnosed based on inclusion criteria with a tilt table. Heart rate was recorded in supine position and then in upright position. Continuous heart rate and BP recording was done every minute for 10 minutes and if patient had symptoms it was noted. Results . During the study period from August 2015–August 2017 we had 42 patients with POTS. This was 7.7% of all patients who had positive tilt table testing during this period. The cohort had 24 males and 18 females. Commonest symptoms were postural giddiness in 18 patients, palpitation on standing and walking in 13 patients and postural syncope in 12 patients. 13 patients had improvement with excess fluid intake, while 29 patients required drug therapy. Conclusion . This is the only series of POTS from India. POTS is not a rare cause of orthostatic intolerance as previously reported. High index of suspicion can help in early identification and treatment of this syndrome.

Association between falls and cardiovascular diseases in the geriatric population.

Objective:To determine the association of cardiovascular diseases with falls in the geriatric population.Methods:Original, Transversal and analytical study. Elderly patients who attend the external consultation of the Geriatrics service, older than 65 years, with falls history, perform comprehensive geriatric assessment to indentify causes of falls in the period from March 2018 to June 2019. We perform measures of central tendency, chi-square test X2 for qualitative variables, we performed linear regression model.Results:A total of 669 patients were included, the analysis shows association with frailty [OR 1.65 (95% CI 1.37-3.77), p <0.05], Heart Failure [OR 1.02, (95% CI, 0.68 - 1.54), p < 0.05 ], the logistic regression analysis with the variables (Fragility, SAH, es: DM2, AMI, Stroke, AF, postural hypotensive syncope, Hypothyroidism, Dyslipidemia, and HF) shows that the probability of falling is 57%.Conclusion:Cardiovascular diseases have a high prevalence in the population studied and increase the risk of falls. Individually analyzed cardiovascular diseases do not show an association with the syndrome of falls in the elderly, except for frailty, which proved to be an independent factor that increases the risk of falls with an OR 1.65. When analyzing them together, the risk of falling increases up to 57%. It is necessary to correctly identify and treat cardiovascular diseases in the elderly.

Family history of associated disorders in patients with postural tachycardia syndrome - Erratum.

INTRODUCTION Postural tachycardia syndrome is more frequently being recognised in adolescents and adults. However, its pathophysiology remains undefined. We evaluated our database for patterns in family history of clinical symptoms and associated disorders in these patients. MATERIALS AND METHODS Patients with postural tachycardia syndrome diagnosed in our clinic between 2014 and 2018 and who were less than 19 years at diagnosis were included. The history was reviewed for family members with postural tachycardia syndrome, dizziness and/or syncope, joint hypermobility with or without hypermobile Ehlers-Danlos syndrome, and autoimmune disorders. Statistical analysis assessed the entire cohort plus differences in gender, presence or absence of joint hypermobility, and presence or absence of familial autoimmune disease. RESULTS A total of 579 patients met inclusion criteria. We found that 14.2% of patients had a family member with postural tachycardia syndrome, with male patients more likely to have an affected family member (20% versus 12.7%, p = 0.04). If the patient also had joint hypermobility, male patients were more likely to have a family member with postural tachycardia syndrome (25% versus 12.6%, p = 0.017), more than one affected family member (7.1% versus 0.74%, p = 0.001), and a family member with joint hypermobility (37.5% versus 23.7%, p = 0.032). Autoimmune disease was seen in 45.1% of family members, but more likely in female patients with concurrent hypermobility (21.1% versus 8.9%, p = 0.035). DISCUSSION This in-depth analysis of associated familial disorders in patients with postural tachycardia syndrome offers further insight into the pathophysiology of the disorder, and informs further screening of family members in these patients.

Family history of associated disorders in patients with postural tachycardia syndrome.

Postural tachycardia syndrome is more frequently being recognised in adolescents and adults. However, its pathophysiology remains undefined. We evaluated our database for patterns in family history of clinical symptoms and associated disorders in these patients. Patients with postural tachycardia syndrome diagnosed in our clinic between 2014 and 2018 and who were less than 19years at diagnosis were included. The history was reviewed for family members with postural tachycardia syndrome, dizziness and/or syncope, joint hypermobility with or without hypermobile Ehlers-Danlos syndrome, and autoimmune disorders. Statistical analysis assessed the entire cohort plus differences in gender, presence or absence of joint hypermobility, and presence or absence of familial autoimmune disease. A total of 579 patients met inclusion criteria. We found that 14.2% of patients had a family member with postural tachycardia syndrome, with male patients more likely to have an affected family member (20% versus 12.7%, p = 0.04). If the patient also had joint hypermobility, male patients were more likely to have a family member with postural tachycardia syndrome (25% versus 12.6%, p = 0.017), more than one affected family member (7.1% versus 0.74%, p = 0.001), and a family member with joint hypermobility (37.5% versus 23.7%, p = 0.032). Autoimmune disease was seen in 45.1% of family members, but more likely in female patients with concurrent hypermobility (21.1% versus 8.9%, p = 0.035). This in-depth analysis of associated familial disorders in patients with postural tachycardia syndrome offers further insight into the pathophysiology of the disorder, and informs further screening of family members in these patients.

Hemodynamic orthostatic dizziness/vertigo: Diagnostic criteria.

This paper presents the diagnostic criteria for hemodynamic orthostatic dizziness/vertigo to be included in the International Classification of Vestibular Disorders (ICVD). The aim of defining diagnostic criteria of hemodynamic orthostatic dizziness/vertigo is to help clinicians to understand the terminology related to orthostatic dizziness/vertigo and to distinguish orthostatic dizziness/vertigo due to global brain hypoperfusion from that caused by other etiologies. Diagnosis of hemodynamic orthostatic dizziness/vertigo requires: A) five or more episodes of dizziness, unsteadiness or vertigo triggered by arising or present during upright position, which subsides by sitting or lying down; B) orthostatic hypotension, postural tachycardia syndrome or syncope documented on standing or during head-up tilt test; and C) not better accounted for by another disease or disorder. Probable hemodynamic orthostatic dizziness/vertigo is defined as follows: A) five or more episodes of dizziness, unsteadiness or vertigo triggered by arising or present during upright position, which subsides by sitting or lying down; B) at least one of the following accompanying symptoms: generalized weakness/tiredness, difficulty in thinking/concentrating, blurred vision, and tachycardia/palpitations; and C) not better accounted for by another disease or disorder. These diagnostic criteria have been derived by expert consensus from an extensive review of 90 years of research on hemodynamic orthostatic dizziness/vertigo, postural hypotension or tachycardia, and autonomic dizziness. Measurements of orthostatic blood pressure and heart rate are important for the screening and documentation of orthostatic hypotension or postural tachycardia syndrome to establish the diagnosis of hemodynamic orthostatic dizziness/vertigo.

Strength and Latency of the HP-SAP Closed Loop Variability Interactions in Subjects Prone to Develop Postural Syncope.

The coupling and latency between heart period (HP) and systolic arterial pressure (SAP) variability can be investigated along the two arms of the HP-SAP closed loop, namely along the baroreflex feedback from SAP to HP, and along the feedforward pathway from HP to SAP. This study investigates the HP-SAP closed loop variability interactions through cross-correlation function (CCF). Coupling strength and delay between HP and SAP variability series were monitored in 13 subjects prone to develop orthostatic syncope (SYNC, 28±9 yrs, 5 males) and in 13 subjects with no history of postural syncope (noSYNC, age: 27±8 yrs, 5 males). Analysis was carried out at rest in supine position (REST) and during head-up tilt (TILT) at 60 degrees. The null hypothesis of HP-SAP uncoupling was tested through a surrogate analysis associating the HP series of a subject with a SAP sequence of a different one. Results showed that during TILT the coupling strength increased along the baroreflex and latency augmented along the mechanical feedforward pathway exclusively in noSYNC subjects. Finally, closed loop HP-SAP interactions were detected in about one third of subjects and the situation of full uncoupling was rarely found. CCF analysis was found to be a straightforward and easily applicable method to investigate HP-SAP control deserving a direct comparison with more sophisticated signal processing tools assessing causality.