Negative Head-up Tilt Table Testing Research Articles

Adenosine plasma levels and adenosine receptor levels determine the outcome of adenosine test and head-up tilt test in syncopal patients with a normal heart

Abstract Background/Introduction The neurohumoral profile underlying the manifestation of reflex syncope remains incompletely understood. Adenosine plasma (ADP) and adenosine receptor (ADR) levels may differentiate the outcomes of head-up tilt table test (HUTT) and adenosine test (ADT) but their role in the diagnostic evaluation of patients with syncope has yet to be determined. Purpose We sought to assess the ADP and ADR levels in patients without structural heart disease who underwent HUTT and ADT tests as part of the diagnostic workup of syncope. We specifically investigated differences in the outcomes of the HUTT and ADT tests as well as to the ADP levels during HUTT. Methods HUTT and ADT were performed as per the standard protocols. ADT was considered positive in the event of asystole >6 seconds or heart block for >10 seconds after intravenous Adenosine 0.15 mg/kg administration in the supine position. ADP levels were assessed at three timepoints during the HUTT: at baseline (supine), immediately after bed tilt and, in cases of a positive HUTT, at the time of syncope. Patients were categorized in quintiles of very low, low, intermediate, high and very high baseline ADP levels. We also assessed the A2A ADR levels of monocytes. Results We prospectively analyzed 124 patients (71 women, age 46.78±21.01 years). ADT was positive in 12.9% of patients and HUTT in 44.4% of patients. Patients with very low baseline ADP levels (lowest quintile) more frequently presented with a positive ADT (odds ratio [OR] 4.08, 95% Confidence Interval [CI] 1.40 to 13.13, p<0.05). Baseline ADP did not differ between patients with positive and negative HUTT. However, patients with vasodepressor response to HUTT exhibited increase in ADP from baseline to bed tilt (0.33±1.03 vs. 0.42±1.14 ppm/Um/L, p<0.05) and in syncope (0.70±1.89, P<0.05), while no difference was noted in patients with cardioinhibitory or mixed response. Patients with positive ADT and negative HUTT had higher ADR levels (221.5±88.56 MFI) as compared to patients with negative ADT and positive HUTT (59.78±83.65 MFI, p<0.05) and to patients with positive ADT and HUTT (33.29±35.77 MFI, p<0.05). Within patients with positive HUTT, those with onset of syncope in the Isoprenaline provocation phase (>20 min) had lower ADR levels (80.88±238.98 vs 89.43±96.08 MFI, p<0.05). Conclusion(s) Baseline ADP levels are related to the outcome of ADT while an ADP increase immediately after bed tilt and in syncope is evident in vasodepressor response to HUTT. Higher ADR levels are related to positive ADT and negative HUTT. Lower ADR levels are associated with more delayed onset of syncope during HUTT. ADP and ADR levels warrant further investigation as they may characterize a subset of patients with specific responses to ADT and HUTT and may be implicated in the pathophysiology of reflex syncope. Funding Acknowledgement Type of funding sources: None.

Repolarization disparity as a predictor of response to Head up Tilt-table Test in pediatric syncope.

Head up Tilt-table Test (HUTT) is a practical examination of the most common type of pediatrics syncope. The electrocardiographic (ECG) changes during this test, show the autonomic defects that cause neuraly-mediated syncope in response to tilting process. All pediatric syncope patients referred to our center in a 1-year period, were included in the study. HUTT was performed and patients were classified into two groups of Negative and Positive HUTT results, and the latter group was subclassified as three subgroups of "vasodepressor", "cardioinhibitory" and "mixed type" responses to HUTT. QT and corrected QT (QTc) dispersion was measured by the baseline standard 12-lead ECG obtained before HUTT. Eighty-six patients with a mean age of 12.19 ± 5.34 were included. Patients with positive HUTT were significantly younger and male gender was more prevalent in this group. Mean QT dispersion was significantly higher in patients with positive HUTT result and also in patients with mixed response to HUTT compared to isolated vasodepressor response. Duration of QTc interval did not change between different study groups. Reciever-Operating-Characteristic (ROC) analysis showed that QT dispersion higher than 32ms is a significant predictor of positive HUTT result (with 92% sensitivity and 98% specificity) and values higher than 40ms can predict the mixed type of response to HUTT (with 84% sensitivity and 63% specificity). Baseline myocardial repolarization disparity significantly correlates with susceptibility to symptomatic vasovagal syncope. This pathology seems to play its role mainly via excessive vagotonic response to sympathetic activation during HUTT process (known as cardioinhibitory response).

Prolongation of Electrocardiographic T Wave Parameters Recorded during the Head-Up Tilt Table Test as Independent Markers of Syncope Severity in Children.

The head-up tilt table test (HUTT) with the upright phase is used to help determine an imbalance of the sympathetic nervous system that is related to abnormal electrocardiographic repolarization in children with vasovagal syncope (VVS) and also in patients with the long QT syndrome (LQTS). The study attempted to evaluate T wave morphology and QT and TpTe (Tpeak–Tend) intervals recorded in ECG during the HUTT for a more accurate diagnosis of children with VVS. The group investigated 70 children with a negative HUTT result: 40 patients with VVS and 30 healthy volunteers without syncope. The RR interval as well as TpTe, and QTc intervals were measured in lead V5 of electrocardiogram (ECG) on admission to the hospital and during three phases of the HUTT. In syncopal children, which included 23 children with bifid or flat T waves and 17 patients with normal T waves in the upright phase, the QTc and TpTe were longer (p < 0.001) compared to the other test phases and longer (p < 0.001) than in the control group, respectively, with the risk of arrhythmias. Only in the control group, the TpTe was shorter (p < 0.001) in the upright phase than in the other tilt phases. The TpTe in the upright phase (>70 ms) was a good discriminator, and was better than the QTc (>427 ms). Prolongation of electrocardiographic TpTe and QT intervals, in addition to the (abnormal T wave morphology recorded during the HUTT, are helpful for identifying VVS children more predisposed to ventricular arrhythmias with a latent risk of LQTS. Further studies are required to assess the value of these repolarization parameters in clinical practice.

The Differences in the Diagnostic Profile in Children with Vasovagal Syncope between the Result of Head-Up Tilt Table Test.

(1) Background: The features characterizing vasovagal syncope (VVS) are an important factor in the correct evaluation of diagnostic risk stratification in children and adolescents. The aim of the study was to determine the value of identifying the clinical characteristics in children with VVS. (2) Methods: We made a retrospective analysis of the medical records of 109 children with diagnosed VVS. We investigated the specific characteristics of syncope in children with VVS including the positive VVS (+) and negative VVS (−) result of the Head-Up Tilt Table Test (HUTT). (3) Results: We did not observe significant differences in the prodromal symptoms of VVS with HUTT response. In addition to typical prodromal symptoms, no difference in statistically reported palpitations (35/109 or 32.1%) and chest discomfort (27/109 or 27.7%) were recorded. Fear–pain–stress emotions as circumstances of syncope were more often reported by children with a negative HUTT (p = 0.02). Cramps–contractures (p = 0.016) and speech disorders (p = 0.038) were significantly higher in the group with negative HUTT. (4) Conclusions: There is a close relationship in the diagnostic profile between the negative and positive results of head-up tilt table test in children with vasovagal syncope.

Early Hemodynamic Changes during Head-Up Tilt Table Testing Can Predict a Neurocardiogenic Response in an African-American Patient Population

Background: Head-up tilt table testing (HUTT) is time-consuming and associated with increased patient morbidity. Hemodynamic changes that occur during the early phase of HUTT may be predictive of neurocardiogenic syncope. Methods: A retrospective chart review was performed in 119 consecutive African Americans ( 57 ± 19) who underwent HUTT for evaluation of syncope of unknown etiology. Positive responses were defined as the development of symptoms linked with a systolic blood pressure (BP) <90 mm Hg, heart rate <50 b.p.m. or sinus arrest >3 s. Hemodynamic variables during the passive phase of HUTT were analyzed and results were then classified as a function of various predictors. Results: Sixty-two subjects (52%) had positive HUTT, and 57 (48%) had negative HUTT. Early changes in BP variables from baseline significantly predicted HUTT responses (p < 0.05). There was also a significant interaction between age and BP. An algorithm based on age and BP was developed which had positive and negative predictive values of 67.7 and 93%, respectively, with an accuracy of 79.8%. Conclusion: A novel algorithm utilizing the patients' age and changes in both systolic and diastolic BP during the early phase of HUTT enables the prediction of HUTT results without the use of vasoactive stimulation, allowing for rapid diagnosis, decreased patient morbidity and reduction in costs.

The relationship of fasting glucose in basic state with the results of head-up tilt table test in children

Objective To explore the relationship of fasting glucose in basic state with the results of head-up tilt table test (HUTT) in children.Methods We choosed 157 cases of children (male 86 and female 71) with unexplained syncope,headache,dizziness and sigh,they were 3 ～ 18 (11.34 ± 3.29) years old and were outpatients or had been hospitalized in the Second Xiangya Hospital of Central South University from Sep 2012 to Feb 2013.The HUTT were carried on after eliminate organic disease of heart,head,bloodvessel and other reasons caused by the above symptoms and obtain written informed consent from participants or guardian.Before HUTI,trace fasting glucose of children would be monitored in based condition.Results (1) Between HUTT negative group (n =63) and HUTT positive group (n =94),there was no significant difference in fasting glucose [(5.40 ± 0.52) mmol/L vs (5.35 ± 0.61) mmoL/L,t =-0.590,P ＞ 0.05].(2) Only 1 case of heart inhibited type vasovagal syncope did not be included in 94 children with HUTT positive.There were no significant differences in fasting glucose between vascular inhibited type vasovagal syncope (n =67) and mixed vasovagal syncope (n =10) and orthostatic tachycardia syndrome (n =16)[(5.34 ±0.54) mmol/L vs (5.07 ±0.64) mmol/L vs (5.49 ±0.81) mmol/L,P ＞0.05].(3) Among 67 cases of vascular inhibitory type vasovagal syncope in children,two kinds induced way of based tilt table test (n =16) and sublingual nitroglycerin tilt table test (n =51) showed no significant differences in fasting glucose [(5.32 ±0.54) mmol/L vs (5.35 ±0.55) mmol/L,t =0.166,P ＞0.05].(4) In two groups of fasting glucose ＜5.5 mmol/L and ≥5.5 mmol/L,HUTT negative rate [37.63％ (35/93) vs 43.75％ (28/64)] and HUTT positive rate [62.37％ (58/93) vs 56.25％ (36/64)] showed no statistical significance (x2 =0.585,P ＞ 0.05).Conclusion Fasting glucose in basic state has no predictive value to HUTT results in children. Key words: Fasting glucose; Head-up tilt table test; Children

Atrial Electromechanical Conduction Delay in Patients with Neurocardiogenic Syncope

We aimed to investigate the presence of atrial electromechanical conduction delay in patients with neurocardiogenic syncope, which was diagnosed with head-up tilt table test (HUTT). A total of 29 patients (mean age: 30.6 ± 15.9 years) with vasovagal syncope, as diagnosed by HUTT, and 23 healthy control subjects (mean age: 34.7 ± 16.3 years) with a negative HUTT were enrolled to the study. Atrial electromechanical conduction delay was defined as the time elapsed from the beginning of the P wave in the electrogardiogram to the beginning of the Am wave in tissue Doppler. There was no statistically significant difference between the groups in terms of interatrial conduction delay, whereas the difference was significant with regard to the right intraatrial electromechanical conduction delay (P < 0.01) and the left intraatrial electromechanical conduction delay (P < 0.0001). There was a negative correlation between the left intraatrial electromechanical conduction delay and the right intraatrial electromechanical conduction delay (r = -0.486, P = 0.001), whereas a positive correlation was present with the interatrial electromechanical conduction delay (r = 0.507, P = 0.001). In this study, the tissue Doppler method revealed that there is left and right intraatrial electromechanical conduction delay in patients with vasovagal syncope. The impact and role of atrial conduction delay as a pathophysiological determinant should be confirmed in further studies.

P-Wave Dispersion: An Indicator of Cardiac Autonomic Dysfunction in Children With Neurocardiogenic Syncope

Neurocardiogenic syncope is the most frequent cause of fainting in childhood and adolescence. Although head-up tilt table testing (HUTT) was previously considered as the reference standard in the diagnosis of syncope, in children with a typical history of reflex syncope, normal physical examination, and electrocardiogram (ECG) are sufficient to cease investigation; however, according to recent reports, TT is indicated in patients in whom this diagnosis cannot be proven by initial evaluation. The hypothesis of this study is that P-wave dispersion (PWD) can be a useful electrocardiographic predictor of cardiac autonomic dysfunction in children with vasovagal syncope (VVS). The study was designed prospectively and included 50 children with positive and 50 children with negative HUTT who presented with at least two previous unexplained episodes of syncope as well as 50 sex- and age-matched healthy children as the control group. All standard 12-lead ECGs were obtained in patients and controls, and the difference between maximum and minimum durations of the P wave was defined as the PWD. A total of 100 children with VVS and 50 healthy controls were evaluated for the study. The P maximum values of HUTT-positive (HUTT[+]) patients were significantly greater than those in the HUTT-negative (HUTT[-]) and control groups(p < 0.05). In addition, mean PWD values were 50.2 ± 18.5, 39.6 ± 11.2 and 32.0 ± 11.2 ms in the HUTT(+), HUTT(-), and control groups, respectively. The difference between groups was statistically significant (p < 0.05). We suggest that PWD is an early sign of cardiac autonomic dysfunction in children with neurally mediated syncope and can be used as a noninvasive electrocardiographic test to evaluate orthostatic intolerance syndromes.

Application of Head-up Tilt Table Testing in Children

We investigated the application of head-up tilt table testing (HUT) and management of neurocardiogenic syncope (NCS) in children, as pediatric studies are limited. Seventy-nine patients (ages 6-18 years) underwent HUT for evaluation of syncope. Patient triggers and premonitory symptoms allowed the clinical diagnosis of NCS or non-NCS. Results were divided into four hemodynamic types (1, 2A, 2B, and 3) according to patient response to HUT. NCS occurred in 65 patients and non-NCS in 14 patients. Isoproterenol infusion significantly increased the sensitivity of the test (from 28% to 45%) and was associated with a slight decrease in the specificity (from 93% to 86%). Subjects in the type 1 group accounted for the majority of responses to the test (69%). There were no complications associated with the test. At follow-up (16.6 ± 9.3 months), the overall recurrence rate was 30.8% but NCS was less severe in most patients. The recurrence rate was similar for patients with a positive or negative HUT and for both pharmacologically and non-pharmacologically treated patients. HUT can be safely performed with a high specificity in children, with the sensitivity of HUT improved by isoproterenol. Therefore, a positive response to treatment is reassuring to the physician and family. NCS is generally a self-limited condition despite a high recurrence rate.

An association between anxiety and neurocardiogenic syncope during head-up tilt table testing.

To study the association between anxiety and neurocardiogenic syncope as determined by head-up tilt table testing (HUT) in men and women with presyncope or syncope, patients with unexplained syncope or presyncope undergoing HUT were asked to complete the Burns Anxiety Inventory (BAI), a validated inventory of 33 questions with responses graded from 0 to 3. HUT consisted of a 30-minute tilt to 60 degrees, which if negative, was repeated with an isoproterenol infusion. A positive HUT was defined as symptomatic hypotension and/or bradycardia. Of the 66 patients who completed the BAI and underwent HUT, 33 were men and 33 were women. The mean age was 57 +/- 18 years (17-91 years). Patients with a positive HUT had a higher BAI score than those with a negative HUT (22 +/- 12 vs 14 +/- 13, P = 0.017). This association was stronger in women with a BAI score of 24 +/- 11 in those with a positive HUT versus 13 +/- 8 in those with a negative HUT (P = 0.005). In contrast, the mean BAI score for men with a positive HUT was 19 +/- 13, as compared to 15 +/- 16 for a negative HUT (P = 0.5). In conclusion, the present study demonstrates a statistical association between anxiety (as determined by BAI) and HUT result. Gender-based analysis revealed a more statistically significant relationship between anxiety and HUT outcome for women as compared to men.

Early Heart Rate Variations During Head-up Tilt Table Testing as a Predictor of Outcome of the Test

Head-up tilt table testing (HUTT) is a useful tool for the diagnosis of unknown origin of syncope. A setback is its duration. This study tries to establish a specific parameter that, according to the heart rate elevation in the test's initial phase, allows a reliable prediction of its outcome. In a prospective study, every patient being under unknown syncope workup was included. A two-phase 20-minute tilt table test was performed. The initial phase was passive, and the second required pharmacological stimulation with isoproterenol. The basal and 5- and 10-minute heart rate values of the passive phase were measured and compared within the group and against negative tests. During a 1-year period, 115 HUTT were performed: 88 were positive and 27 negative. The negative HUTT patients had an increase in HR of 5.05 (+/- 13.5) beats/min at 5 minutes, and 5.79 (+/- 12.9) beats/min at 10 minutes (P = 0.2). Those with a positive HUTT had an increase of 9.05 (+/- 14.5) beats/min at 5 minutes, and of 10 (+/- 13.4) beats/min at 10 minutes (P < 0.001). There were no significant changes in HR when comparing positive to negative HUTT. There is no specific number that allows predication of outcome early in HUTT. Within the group, variations are important. Only a group tendency can be established, which strongly correlates with the results obtained during the test.

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.