Positive Head-up Tilt Table Research Articles

Postural orthostatic tachycardia syndrome and other autonomic dysfunctions following COVID-19: Incidence, characteristics, and associated factors.

Long-COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction, especially postural orthostatic tachycardia syndrome (POTS) following COVID-19. However, there is a lack of information regarding the incidence and associated factors in Asian population. A retro-prospective study was conducted to evaluate patients with symptoms suggestive of POTS or other autonomic dysfunctions. These symptoms last at least 3 months after PCR-proven COVID-19. Exclusion criteria were age under 18 years old, pregnancy, and pre-COVID-19 autonomic dysfunction symptoms. Patients with a symptom severity score greater than two were assessed with blood tests, 24-h Holter, 24-h ambulatory blood pressure, echocardiogram, and head-up tilt table (HUTT). Seven hundred ninety-three patients were interviewed at 146 ± 37 days after COVID-19. The majority of patients were middle-aged females (53%). Of those, 15 patients had the symptom severity score greater than 2. Out of those 15 patients, 12 had positive HUTT (1 demonstrating POTS, 10 neurocardiogenic syncope, and 1 orthostatic hypotension). Among those with positive HUTT patients, C-reactive protein (CRP) was significantly higher (OR 1.01; p-value 0.041). Fatigue and dyspnea on exertion were the two most complaint symptoms. This study shows the incidence of autonomic dysfunction and POTS is 1.5% (12/793) and 0.1% POTS (1/793), respectively, in a primary care setting (among general post-COVID-19 patients). The most common symptoms for these patients were fatigue and dyspnea.

Postural orthostatic tachycardia syndrome (POTS) and other autonomic dysfunction following COVID-19 infection: incidence, characteristic and associating factors

Abstract Background Long-COVID syndrome has become a new health concern. Many major clinical centers worldwide have experienced more patients with symptoms suggestive of autonomic dysfunction especially Postural Orthostatic Tachycardia syndrome (POTS). These patients were previously diagnosed with COVID19. However, there is lack of incidence and associating factors in Asian population. Objective This study investigated the incidence, associating factors and clinical features in patients with new-onset symptoms suggesting POTS or other autonomic disorders following COVID-19 infection. Methods We conducted a retro-prospective study to evaluate patients from COVID-19 outpatient clinic who have symptoms suggestive of POTs or other autonomic dysfunctions. These symptoms must last at least three months after PCR proven COVID 19 infections. Exclusion criteria were age < 18 years old, pregnancy and pre COVID-19 infection symptoms. Patients with symptoms severity score greater than two were assessed with blood tests, 24-hour Holter, 24-hour ambulatory blood pressure, echocardiogram and underwent head-up tilt table (HUTT). Results 793 patients were interviewed at a mean of 146± 37 days after COVID-19 infection. Majority of patients are middle-aged female. 15 patients with symptoms severity score >2 were investigated. Out of those 15 patients, 12 have positive HUTT (1 demonstrating POTS, 10 neuro cardiogenic syncope, and 1 orthostatic hypotension). Among those positive HUTT patients, C-reactive protein (CRP) is significantly higher (OR 1.01; p-value 0.041). Fatigue and orthostatic intolerance are the two most complaint symptoms. All patients with positive HUTT have non dipping pattern on 24-hour ambulatory BP monitoring. Conclusions This study demonstrates incidence of 1.5% (12 out of 793) autonomic dysfunction and 0.1% POTS (1 out of 793) among post COVID-19 outpatient cases . Associating factor includes high CRP during infection. Most complaint symptoms are fatigue and orthostatic intolerance.Patient flow diagramType and severity of symptoms

Selective serotonin reuptake inhibitors for debilitating vasovagal syncope: looking for copper and finding gold

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite its benign course, recurrent and unpredictable vasovagal syncope (VVS) may be disabling. Even though a non-pharmacological approach is generally regarded as first-line, a variety of drugs might also be of use. In this respect, the clinical value of selective serotonin reuptake inhibitors (SSRIs) is still a matter of debate. Purpose To perform a meta-analysis aimed at evaluating the extent to which SSRIs might reduce VVS recurrences in susceptible patients. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar for prospective studies, addressing the effect of SSRIs on the recurrence rate of VVS in predisposed patients, published up until December 31st, 2020. In order to be included in the quantitative analysis, studies were required to encompass a positive head-up tilt table (HUTT) test for VVS diagnosis and a minimum patient follow-up of 6 months. The primary endpoint was recurrent spontaneous VVS, whereas secondary endpoints included the efficacy outcome of HUTT test-induced VVS and the safety outcome of drug discontinuation for adverse effects. Randomized controlled trials (RCTs) and studies including the most represented SSRI drug were further investigated separately, with respect to the primary endpoint. Study-specific odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model. Results 3 RCTs (2 placebo-controlled and 1 both placebo- and active-controlled) and 1 non-randomized prospective study, encompassing 222 and 127 patients, respectively, were regarded as eligible for quantitative evaluation. Patient follow-up ranged between 6 and 24 months. 131 patients were allocated to the SSRI arm, which featured fluoxetine as the most represented element (97 cases). The absolute number of events for each outcome may be reported as follows: primary efficacy endpoint, 57; secondary efficacy endpoint, 68 (only 2 RCTs reporting); secondary safety endpoint, 4 (only 2 RCTs reporting). In the main analysis, SSRIs were not found to significantly reduce VVS recurrence rate (OR 0.48, 95% CI 0.13-1.81, P 0.28, i2 74%). This null result was, however, single-handedly driven by the only non-randomized study included (OR 4.5, 95% CI 0.85-23.8). Likewise, fluoxetine was not able to significantly reduce the primary efficacy endpoint (OR 0.7, 95% CI 0.12-4.12, P 0.7, i2 78%), while SSRIs only numerically cut HUTT test-induced VVS events (OR 0.66, 95% CI 0.24-1.84, P 0.43, i2 59%). Nevertheless, when only RCTs are considered, SSRIs exerted a meaningful reduction in VVS recurrence rate, with no heterogeneity (OR 0.25, 95% CI 0.12-0.5, P 0.0001, i2 0%). In addition, drug discontinuation for safety reasons was rare and comparable between the SSRI and the placebo arms (OR 1.51, 95% CI 0.21-10.74, P 0.59, i2 0%). Conclusion SSRIs do represent one more safe pharmacological option to reduce syncope recurrences in patients with otherwise refractory VVS. Abstract Figure.

POLYMORPHISMS IN β-ADRENERGIC RECEPTORS ARE ASSOCIATED WITH INCREASED RISK TO HAVE A POSITIVE HEAD-UP TILT TABLE TEST IN PATIENTS WITH VASOVAGAL SYNCOPE.

Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and β-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5' exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. These results suggest that some polymorphisms of the β-AR genes could contribute to a positive tilt test in patients with VVS.

Novel functional advanced echocardiography for the assessment of myocardial mechanics in children with neurocardiogenic syncope \u2013 a blinded prospective speckle tracking head-up tilt-table challenge study

BackgroundData on left ventricular (LV) function in patients with neurocardiogenic syncope (NS) is conflicting in adults and lacking in children. The aim of this study was to analyze LV myocardial performance in children with NS at rest and during head-up tilt-table (HUTT) testing.MethodsThis is the first study to combine HUTT and speckle-tracking echocardiography (STE) in children with NS. 43 consecutive normotensive pediatric patients with NS (mean age 13.9 ± 2.6 years, 51% female) and 41 sex- and age-matched healthy controls were included in the study. The study groups consisted of 21 patients with a positive HUTT reaction (HUTT+) and 22 with a negative HUTT reaction (HUTT-). STE was used to analyze peak systolic LV myocardial strain and strain rate.ResultsConventional echocardiographic parameters were similar in all analyzed groups. When compared to healthy controls, children with NS had depressed levels of circumferential strain rate (p = 0.032) and significantly depressed longitudinal strain rate (p < 0.001) at rest. Interestingly, during HUTT testing LV global strain and strain rate were similar in both groups. LV strain rate was lowest in HUTT+ followed by HUTT- and control subjects both at rest and during HUTT.ConclusionsResting LV longitudinal strain rate is attenuated in children with NS, especially in those with a positive HUTT response. This is further evidence that NS patients feature altered cardiac mechanics rendering them prone to vasovagal perturbations that can ultimately result in collapse.Trial registrationWitten/Herdecke University ethics committee clinical study number: UWH-73-2014.

A single-center randomized controlled trial observing the safety and efficacy of modified step-up graded Valsalva manoeuver in patients with vasovagal syncope.

Non-pharmacological therapies, especially the physical maneuvers, are viewed as important and promising strategies for reducing syncope recurrences in vasovagal syncope (VVS) patients. We observed the efficacy of a modified Valsalva maneuver (MVM) in VVS patients. 72 VVS patients with syncope history and positive head-up tilt table testing (HUTT) results were randomly divided into conventional treatment group (NVM group, n = 36) and conventional treatment plus standard MVM for 30 days group (MVM group, n = 36). Incidence of recurrent syncope after 12 months (6.5% vs. 41.2%, P<0.01) and rate of positive HUTT after 30 days (9.7% vs.79.4%, P<0.01) were significantly lower in MVM group than in NVM group. HRV results showed that low frequency (LF), LF/ high frequency (HF), standard deviation of NN intervals (SDNN) and standard deviation of all 5-min average NN intervals (SDANN) values were significantly lower in the NVM and MVM groups than in the control group at baseline. After 30 days treatment, LF, LF/HF, SDNN, SDANN values were significantly higher compared to baseline in MVM group. Results of Cox proportional hazard model showed that higher SDNN and SDANN values at 30 days after intervention were protective factors, while positive HUTT at 30 days after intervention was risk factor for recurrent syncope. Our results indicate that 30 days MVM intervention could effectively reduce the incidence of recurrent syncope up to 12 months in VVS patients, possibly through improving sympathetic function of VVS patients.

Genome-Wide Association Study of Copy Number Variations in Patients with Familial Neurocardiogenic Syncope.

Neurocardiogenic syncope (NCS) is the most frequent type of syncope characterized by a self-limited episode of systemic hypotension. In this study, we conducted the first genome-wide association study testing copy number variations for association with NCS. Study population consisted of 107 consecutive patients with recurrent syncope and positive head-up tilt table testing. Four families with NCS were selected for CNV analysis. Affymetrix GeneChip(®) SNP 6.0 array was used for CNV analysis. Data and statistical analysis were performed with Affymetrix genotyping console 4.0 and GraphPad Prism v6. Positive family history of NCS was present in 19.6% (n=21) in our study population (n=107). Twenty-six CNV regions were found to be significantly altered in families with NCS (P<0.05). Several CNVs were identified in families with NCS. Further studies comprising wider study population are required to determine the effect of these variations on NCS development.

Evaluation of the effect of radiofrequency catheter ablation on autonomic function in patients with atrioventricular nodal reentrant tachycardia by head-up tilt table test.

Background:One of the recommended treatments for atrioventricular nodal reentrant tachycardia (AVNRT), is radiofrequency catheter ablation (RFCA). However, RFCA may affect the autonomic system. This study aims to evaluate the effect of RFCA on autonomic system in patients with PSVT by head-up tilt table (HUTT) test.Materials and Methods:In a before–after study, 22 patients with PSVT were enrolled. Data were collected with a data collection form that included two parts. Electrocardiogram (ECG), echocardiogram, 24-h Holter monitoring, HUTT test, heart rate variability (HRV) indexes, and symptoms of all patients were recorded 24 h before and 1 month after the ablation. Wilcoxon, McNemar, Mann–Whitney U, and Chi-square tests were used to analyze the data.Results:Of the total 22 patients, 31.8% were male and 68.2% were female. There were significant differences in heart palpitation (P < 0.0001) and non-specific symptoms (P = 0.031) and no significant difference in head-up tilt test results and HRV indices before and after RFCA. The results showed that there were no significant differences in specific and non-specific symptoms in patients with AVNRT with positive and negative HUTT before and after RFCA.Conclusions:The observed difference in heart palpitation and non-specific symptoms emphasized the role of AVNRT in causing these symptoms. Autonomic dysfunction is more probably an accompanying condition of AVNRT than causing symptoms. We could not find any significance in the results of HUTT after RFCA. HUTT cannot determine or predict the symptoms after RFCA.

Effect of Head-Up Tilt-Table Testing on Left Ventricular Longitudinal Strain in Patients With Neurocardiogenic Syncope

Recent studies have shown conflicting data regarding left ventricular (LV) function in patients with neurocardiogenic syncope, with some investigators reporting a marked decrease in LV end-systolic wall stress and stress-corrected fractional shortening. We sought to determine the characteristics of resting LV deformation in patients with neurocardiogenic syncope by selective motion tracking of subendocardial and subepicardial regions using speckle tracking echocardiography. We assessed resting LV function in 82 patients undergoing head-up tilt-table (HUTT) testing. Patients were divided into 3 groups based on a positive HUTT test with associated co-morbid conditions (n= 30), no associated co-morbid conditions (n= 30), or negative HUTT results (n= 22). LV longitudinal, circumferential, and radial strains were obtained by speckle tracking echocardiography of subendocardial and subepicardial regions in each group and compared with resting LV deformation in 20 healthy control subjects. Compared with endocardial longitudinal strain in control subjects, that in patients with positive HUTT results was attenuated, irrespective of co-morbid conditions (p <0.05). Circumferential and radial strains did not differ among groups. On multivariate logistic regression analysis, endocardial longitudinal strain was an independent predictor (odds ratio, 1.16; p= 0.01) of positive HUTT test results. In conclusion, resting LV longitudinal strain is attenuated in patients with positive HUTT test results. Overall, these results may suggest that an increase in resting LV contractility is not a prerequisite for development of neurocardiogenic syncope.

Prevalence and Clinical Factors of Anxiety and Depression in Neurally Mediated and Unexplained Syncope

PurposeSeveral studies have demonstrated that psychiatric disorders such as anxiety, depression and panic attack are associated with syncope, especially vasovagal and unexplained syncope (US). The aim of this study was to compare the prevalence of anxiety and depression between patients with neurally mediated syncope (NMS) and US and to investigate the clinical factors associated with anxiety and depression.Materials and MethodsBetween January 2009 and March 2010, 383 patients with syncopal episodes completed a Hospital Anxiety and Depression Scale questionnaire to assess symptoms of anxiety and depression. Inclusion criteria were NMS and US. Exclusion criteria were cardiac syncope, orthostatic hypotension and other disorders mimicking syncope. After exclusion, 199 patients were included.ResultsThere were 176 (88.4%) NMS patients and 23 (11.6%) US patients. The prevalence of abnormal anxiety and depression were not significantly different between the NMS and US groups (10.2% vs. 8.7%, p=0.99; 8.5% vs. 17.4%, p=0.24). Clinical factors associated with anxiety were female gender (p=0.01) and six or more recurrent syncopal episodes (p=0.01) by univariate analysis. The only factor associated with abnormal anxiety score (OR=20.26, 95% CI: 1.4-291.6, p=0.01) was more than six recurrent syncopal episodes, while a positive head-up tilt table testing response was inversely associated with abnormal depression score (OR=0.28, CI: 0.08-0.97, p=0.04) in the multiple logistic regression analysis.ConclusionAnxiety was associated with frequent syncopal episodes. Thus, anxiety might be considered in the management of syncope patients.

The relationship between carotid sinus hypersensitivity, orthostatic hypotension, and vasovagal syncope: a case-control study

Previous uncontrolled studies reported an overlap between carotid sinus hypersensitivity (CSH), vasovagal syncope (VVS), and orthostatic hypotension (OH). We conducted a case-control study evaluating this relationship in a large patient cohort. The electronically stored continuous electrocardiograph and blood pressure (BP) measurements for active stand and head-up tilt-table (HUT) tests of 302 consecutive patients investigated with carotid sinus massage (CSM) were analysed. Carotid sinus hypersensitivity was defined as >or=3 s asystole and/or systolic BP (SBP) drop of >or=50 mmHg during CSM. Orthostatic hypotension was defined as BP reductions of >or=20 mmHg systolic or of >or=10 mmHg diastolic, whereas VVS was diagnosed with a positive HUT test. There was no significant difference in the number of subjects with OH (57 vs. 55%; P = 0.778) or HUT-positive VVS (45 vs. 47%; P = 0.828) between cases with CSH and controls without CSH. Carotid sinus hypersensitivity subjects had significantly larger SBP reduction (P = 0.039) and longer time to nadir (P = 0.007) during active stand, and trends to vasodepressor (P = 0.071) and dysautonomic responses to HUT (P = 0.151). Carotid sinus hypersensitivity, OH, and VVS are common conditions affecting patients with syncope and falls which are likely to co-exist in such individuals. The differences in haemodynamic response patterns to active stand and HUT in CSH subjects could be the result of an age-associated delay in sympathetic responses.

Preliminary Observations on the Effect of Amitriptyline Treatment in Preventing Syncope Recurrence in Patients with Vasovagel Syncope

Vasovagal syncope is a common and challenging problem that may result in injury and causes substantial anxiety among patients and their relatives. However, treatment of vasovagal syncope with standard pharmacologic approaches is not satisfactory. The aim of this study is to investigate the effect of amitriptyline, a tricyclic antidepressant drug, by using its anticholinergic effects in preventing syncopal episodes in patients with vasovagal syncope. In this study, 74 patients (mean age 24 +/- 1.9 years, 26 male) with a history of recurrent syncope and baseline positive head-up tilt table test (syncope or presyncope) were included. Oral amitriptyline treatment was given to all patients, with a starting dose of 10 mg once a day. Head-up tilt table test was performed in all patients 4 weeks after the treatment started. Patients were followed up clinically for 6 months. After 4 weeks, during head-up tilt table test in 69 patients (93%), syncope or presyncope was not seen and test was assumed as negative. At the end of the 6th month, 67 patients (91%) were free of symptoms. Only two patients (0.3%) did not tolerate amitriptyline due to side effects. Oral amitriptyline can be used in the prevention of recurrent episodes of vasovagal syncope safely. However, randomized controlled studies are essential to assess the real effectiveness of this therapy.

Driving safety among patients with neurocardiogenic (vasovagal) syncope.

Neurocardiogenic syncope is one of the most common causes of syncope. However, the important issue of driving related injury due to syncope in this population is not well defined. Risk of injury due to syncope while driving and driving behavior was evaluated in 155 consecutive patients (92 women and 63 men; mean age 49 +/- 19 years) with history of syncope in whom hypotension and syncope or presyncope could be provoked during head-up tilt testing. Patients with syncope and positive head-up tilt table test were treated with pharmacological therapy. All participants were asked to fill out a detailed questionnaire regarding any driving related injuries and their driving behavior before tilt table testing and during follow-up. Prior to head-up tilt testing two patients had syncope while driving, and one of these patients had syncope related injury during driving. The mean duration of syncopal episodes was 50 +/- 14 months (range 12-72 months). Of the 155 patients, 52 (34%) had no warning prior to syncope, while 103 (6%) had warning symptoms such as dizziness prior to their clinical syncope. Following a diagnosis of neurocardiogenic syncope established by head-up tilt testing, six patients stopped driving on their own. During a median follow-up of 22 months recurrent syncope occurred in five (3.2%) patients. No patient had syncope or injury during driving. In conclusion, syncope and injury while driving in patients with neurocardiogenic syncope is rare. The precise mechanism of this is unclear but may be related to posture during driving. Consensus among the medical community will be needed to provide specific guidelines in these patients.

Positive head-up tilt table test in patients with the long QT syndrome.

Syncope in patients with the long QT syndrome is commonly attributed to a ventricular arrhythmia (torsades de pointes). The susceptibility of patients with the long QT syndrome (LQTS) to neurally mediated syncope is currently unknown. Head-up tilt table testing (70 degrees) was performed in six patients with the long QT syndrome and a history of syncope. All patients had syncope with a mixed response. The RR interval was significantly decreased 2 min before the onset of syncope (980 +/- 125 ms vs 630 +/- 91 ms, P=0.003), and significantly increased during syncope (983.17 +/- 224.71; P=0.006). Non-significant changes in QT intervals were observed. Baseline QT was 513 +/- 86 ms and decreased to 450 +/- 59 ms 2 min before the onset of syncope (P=0.11). Although not statistically significant, QT intervals during syncope were longer than at 2 min before syncope (485 +/- 85 ms vs 450 +/- 59 ms; P=0.29). Our results suggest that patients with the LQTS are susceptible to neurally mediated syncope. Whether this susceptibility differs from control populations remains unresolved. From a clinical standpoint, neurocardiogenic syncope should be considered a diagnostic alternative in patients with LQTS.

Efficacy and Safety of Clonazepam in Refractory Neurally Mediated Syncope

Neurally mediated syncope is a complex syndrome that is often difficult to manage using currently available treatment strategies. The efficacy and safety of clonazepam was evaluated in 35 patients with refractory neurally mediated syncope. All patients had syncope (n = 33) or disabling presyncope (n = 2) and a positive head-up tilt table test (HUTT) despite treatment with one or more of the following therapies: beta-blocker, high-salt diet, fludrocortisone, elastic compression stockings, and disopyramide. Clonazepam was initiated at 0.5 mg/day and titrated in 0.25-0.5 mg/day increments for symptom control. Early (first 8 weeks) symptomatic response was achieved in 31 of 35 (89%) patients. Early HUTT reverted to negative in 29 of 35 (83%) patients. Two patients discontinued clonazepam during early follow-up due to side effects. Thirty-three patients received long-term clonazepam therapy. Twenty-five patients had late HUTT with 21 remaining negative. Of the eight patients who did not have late HUTT, one patient discontinued clonazepam prior to HUTT due to side effects. Seven patients refused late HUTT. All seven patients achieved symptomatic control on clonazepam with two requiring dose titration. Of the 21 patients with a negative late HUTT, 18 achieved symptomatic control with two of these patients requiring dose titration. Two patients who had only partial symptom control despite dose titration achieved total symptomatic control with the addition of disopyramide and beta-blockers. Two patients with a negative late HUTT discontinued clonazepam due to side effects. One patient had been symptomatically controlled while the other had recurrent symptoms with dose limiting side effects occurring after clonazepam dose titration. In the 4 patients with a positive late HUTT, 2 patients were symptomatically controlled, 1 patients required combination therapy with a beta-blocker to achieve symptomatic control, and 1 patient discontinued therapy due to side effects. Overall, 29 of 35 (83%) patients continue to receive clonazepam with symptom control. Based on intention-to-treat HUTT results, 21 of 35 (60%) patients were responders. Four patients required clonazepam dose titration and three required combination therapy with clonazepam plus disopyramide and/or a beta-blocker to achieve control. Clonazepam was discontinued in 6 patients, 5 for side effects and 1 following a transient ischemic attack. Clonazepam appears to be an effective therapeutic alternative in patients with refractory neurally mediated syncope. Based on our preliminary findings, a placebo controlled evaluation of clonazepam in neurally mediated syncope is warranted.