Mechanisms of tilt-induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope.

Upright tilt table testing has been used to test for vasovagal syncope (VVS) but can result in "false positives" in which tilt-induced fainting (tilt+) occurs in the absence of real-world fainting. Tilt+ occurs in healthy volunteers and in patients with postural tachycardia syndrome (POTS) and show enhanced susceptibility to orthostatic hypotension. We hypothesized that the mechanisms for hypotensive susceptibility differs between tilt+ healthy volunteers (Control-Faint (N = 12)), tilt+ POTS patients (POTS-Faint (N = 12)) and a non-fainter control group of (Control-noFaint) (N = 10). Subjects were studied supine and during 70° upright tilt while blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR), were measured continuously. Impedance plethysmography estimated regional blood volumes, flows, and vascular resistance. Heart rate was increased while central blood volume was decreased in both Faint groups. CO increased in Control-Faint because of reduced splanchnic vascular resistance; splanchnic pooling was similar to Control-noFaint. Splanchnic blood flow in POTS-Faint decreased and resistance increased similar to Control-noFaint but splanchnic blood volume was markedly increased. Decreased SVR and splanchnic arterial vasoconstriction is the mechanism for faint in Control-Faint. Decreased CO caused by enhanced splanchnic pooling is the mechanism for faint in POTS-Faint. We propose that intrahepatic resistance is increased in POTS-Faint resulting in pooling and that both intrahepatic resistance and splanchnic arterial vasoconstriction are reduced in Control-Faint resulting in increased splanchnic blood flow and reduced splanchnic resistance.

Tilt testing and what you should know about it - Experience with 835 consecutive patients with syncope of unknown origin.

BACKGROUND: Numerous tilt testing protocols with and without a preceding passive phase or the administration of nitrates have already been investigated. However, a truely standardized method for the investigation does not yet exist. METHODS AND RESULTS: A total of 835 consecutive patients who underwent tilt testing between January 2005 and March 2015 were included in this study. Results of a passive tilt test (PTT), a nitrate-stimulated tilt test (NSTT) with a preceding passive phase of 20 min, or an early nitrate-stimulated tilt test (ENSTT) without a preceding passive phase were compared and analyzed retrospectively in 735 patients. In addition, a further 100 consecutive patients were prospectively randomized 1:1 to compare NSTT and ENSTT. In the retrospective analysis, 38% of the patients in the ENSTT group had a positive test response compared with 45% in the NSTT group and only 27% in the PTT group (p = 0.0002). In the prospective study, 34% of the patients had a positive test response in the ENSTT group compared with 42% in the NSTT group (p = 0.537). The mean duration to a positive test response was significantly shorter in the ENSTT group (retrospective and prospective p < 0.001). The nitrate-stimulated groups did not differ significantly with respect to the hemodynamic characteristics of a positive test response (retrospective: p = 0.773; prospective: p = 0.086). CONCLUSION: Due to the rate of positive test response being comparable to other protocols and its significantly shorter test duration, nitrate-stimulated tilt testing without a preceding passive tilt test may be favored for use in a busy clinical practice.

Reappraisal of the Utility of the Tilt-table in the Investigation of Venous Disease†.

OBJECTIVES: Without gravity opposing drainage, most venous diseases would not exist. Therefore, manoeuvres that assess venous function should include gravity. The aim was to "dose" gravity in subjects using static positions and dynamic angulations on a tilt-table and to assess its effects with air plethysmography (APG) and duplex ultrasound over the femoral vein. METHODS: Three groups (providing n = 11 legs each) were compared. (a) A control group, without clinical or duplex evidence of venous disease. (b) An obstruction group, with past iliofemoral deep vein thrombosis. (3) A reflux group, with primary varicose veins. A manually operated tilt-table ranging from -70° to 40° in the Trendelenburg position provided rapid tilting (<3 s). The changes in calf volume at -70° (almost standing), -45° (reclining), and 40° (legs-up) were recorded with APG, as well as the rate and duration of the changes. The minor diameter of the femoral vein was recorded at the three tilt positions. RESULTS: The results were expressed as median (interquartile range). The total working venous volume (mL) in the reflux group was significantly increased: 202 (180-240) mL versus the controls at 138 (119-198) mL, p = .008, and versus the legs with obstruction at 117 (80-154) mL, p < .0005. The venous drainage index (VDI) in mL/second in the obstructed group was significantly reduced: 7 (6-9.6) mL/second, versus the controls at 17.4 (13.9-27.2) mL/second, p < .0005, and versus the legs with varicose veins at 28.1 (25.4-34.4) mL/second, p < .0005. The venous filling index (VFI) in mL/second in the reflux group was significantly increased: 8.1 (4.2-10) mL/second versus the controls at 1.8 (1-2.1) mL/second, p < .0005. The VDI cut-off point discriminating obstruction was ≤10.8 mL/second and the VFI discriminating reflux was ≥ 2.9 mL/second. The femoral vein diameter was reduced significantly with increasing leg elevation. CONCLUSIONS: Manoeuvres using APG on a tilt-table have the potential to quantify the contributions of global obstruction and reflux (mL/second) in patients with venous disease.

Test-retest reliability and four-week changes in cardiopulmonary fitness in stroke patients: evaluation using a robotics-assisted tilt table.

BACKGROUND: Exercise testing devices for evaluating cardiopulmonary fitness in patients with severe disability after stroke are lacking, but we have adapted a robotics-assisted tilt table (RATT) for cardiopulmonary exercise testing (CPET). Using the RATT in a sample of patients after stroke, this study aimed to investigate test-retest reliability and repeatability of CPET and to prospectively investigate changes in cardiopulmonary outcomes over a period of four weeks. METHODS: Stroke patients with all degrees of disability underwent 3 separate CPET sessions: 2 tests at baseline (TB1 and TB2) and 1 test at follow up (TF). TB1 and TB2 were at least 24 h apart. TB2 and TF were 4 weeks apart. A RATT equipped with force sensors in the thigh cuffs, a work rate estimation algorithm and a real-time visual feedback system was used to guide the patients' exercise work rate during CPET. Test-retest reliability and repeatability of CPET variables were analysed using paired t-tests, the intraclass correlation coefficient (ICC), the coefficient of variation (CoV), and Bland and Altman limits of agreement. Changes in cardiopulmonary fitness during four weeks were analysed using paired t-tests. RESULTS: Seventeen sub-acute and chronic stroke patients (age 62.7 ± 10.4 years [mean ± SD]; 8 females) completed the test sessions. The median time post stroke was 350 days. There were 4 severely disabled, 1 moderately disabled and 12 mildly disabled patients. For test-retest, there were no statistically significant differences between TB1 and TB2 for most CPET variables. Peak oxygen uptake, peak heart rate, peak work rate and oxygen uptake at the ventilatory anaerobic threshold (VAT) and respiratory compensation point (RCP) showed good to excellent test-retest reliability (ICC 0.65-0.94). For all CPET variables, CoV was 4.1-14.5 %. The mean difference was close to zero in most of the CPET variables. There were no significant changes in most cardiopulmonary performance parameters during the 4-week period (TB2 vs TF). CONCLUSIONS: These findings provide the first evidence of test-retest reliability and repeatability of the principal CPET variables using the novel RATT system and testing methodology, and high success rates in identification of VAT and RCP: good to excellent test-retest reliability and repeatability were found for all submaximal and maximal CPET variables. Reliability and repeatability of the main CPET parameters in stroke patients on the RATT were comparable to previous findings in stroke patients using standard exercise testing devices. The RATT has potential to be used as an alternative exercise testing device in patients who have limitations for use of standard exercise testing devices.

Calibrated variability of muscle sympathetic nerve activity during graded head-up tilt in humans and its link with noradrenaline data and cardiovascular rhythms.

Muscle sympathetic nerve activity (MSNA) variability is traditionally computed through a low-pass filtering procedure that requires normalization. We proposed a new beat-to-beat MSNA variability computation that preserves dimensionality typical of an integrated neural discharge (i.e., bursts per unit of time). The calibrated MSNA (cMSNA) variability technique is contrasted with the traditional uncalibrated MSNA (ucMSNA) version. The powers of cMSNA and ucMSNA variabilities in the low-frequency (LF, from 0.04 to 0.15 Hz) band were computed with those of the heart period (HP) of systolic and diastolic arterial pressure (SAP and DAP, respectively) in seven healthy subjects (age, 20-28 years; median, 22 years; 5 women) during a graded head-up tilt. Subjects were sequentially tilted at 0°, 20°, 30°, 40°, and 60° table inclinations. The LF powers of ucMSNA and HP variabilities were expressed in normalized units (LFnu), whereas all remaining spectral markers were expressed in absolute units. We found that 1) the LF power of cMSNA variability was positively correlated with tilt angle, whereas the LFnu power of the ucMSNA series was uncorrelated; 2) the LF power of cMSNA variability was correlated with LF powers of SAP and DAP, LFnu power of HP and noradrenaline concentration, whereas the relationship of the LFnu power of ucMSNA variability to LF powers of SAP and DAP was weaker and that to LFnu power of HP was absent; and 3) the stronger relationship of cMSNA variability to SAP and DAP spectral markers compared with the ucMSNA series was confirmed individually. The cMSNA variability appears to be more suitable in describing sympathetic control in humans than traditional ucMSNA variability.

Venepuncture during head-up tilt testing in patients with suspected vasovagal syncope ­ implications for the test protocol.

BACKGROUND AND PURPOSE: Head-up tilt (HUT) testing is a widely used diagnostic tool in patients with suspected vasovagal syncope (VVS). However, no gold standard exists for this examination and the various protocols used have a limited sensitivity and specificity. Our aim was to determine the sensitivity of a sequential HUT testing protocol including venepuncture (VP) and sublingual nitroglycerin application. METHODS: This was a retrospective analysis of the diagnostic gain of a sequential HUT testing protocol including VP applied 10 min after the start of HUT testing and sublingual application of nitroglycerin 20 min after the start of the test protocol in 106 patients with a final diagnosis of VVS. The sensitivity of the test protocol was compared between patients with positive and negative history for VP induced VVS. RESULTS: Overall, pre-syncope or syncope occurred in 68 patients (64.2%). Only 17% of all patients fainted spontaneously within 10 min of passive HUT. Another 39.6% fainted within 20 min. Application of nitroglycerin after 20 min of HUT evoked syncope in another 7.5% until the end of 45 min of HUT. The sensitivity of the test protocol for evoking (pre-)syncope was 94.4% in patients with a positive history for VP associated VVS and 58% in patients with a negative history (P < 0.01**); 85.7% of patients with a positive history and 42.9% of patients with a negative history fainted within 20 min of HUT testing (P < 0.01**). CONCLUSIONS: Implementation of VP in sequential HUT testing protocols allows the sensitivity of HUT testing to be increased, especially in patients with a positive history for VP associated VVS.

Twenty-eight years of research permit reinterpretation of tilt-testing: hypotensive susceptibility rather than diagnosis.

There is growing scepticism over utility of tilt-testing for syncope diagnosis, which has been shown unable to distinguish vasovagal from other syncope, especially cardiac, despite its acceptable sensitivity and specificity in true positive and negative subjects. The new interpretation is that the test reveals a susceptibility to reflex hypotension, which may exist in coincidence with any cause of syncope. This implies an important change in patient management including selecting effective therapy, in particular in guiding pacemaker therapy in patients affected by reflex syncope.

Symptoms predictive of postural tachycardia syndrome (POTS) in the adolescent headache patient.

OBJECTIVE: To identify symptoms that may predict postural tachycardia syndrome (POTS) among adolescent patients with headache and lightheadedness referred for tilt table testing. BACKGROUND: Individuals with POTS can have a variety of symptoms that impair quality of life. The specific symptoms that help to distinguish the POTS patient in an adolescent headache population have not been determined. METHODS: A group of symptoms was compared among 70 adolescent patients with headache and lightheadedness referred to a pediatric headache clinic for tilt table testing. Every patient completed a symptom questionnaire prior to the tilt table test. The chi-square test was used to compare questionnaire responses between patients found to have POTS and those who did not have POTS. Thirteen symptoms were analyzed. Symptoms that differed statistically between groups were further assessed for sensitivity, specificity, and diagnostic predictive values. RESULTS: Thirty-seven (53%) patients met diagnostic criteria for POTS. Several symptoms differed between the patients found to have POTS and those without POTS. Headache type was not predictive. Vertigo and evening exacerbation of headaches had P values <.05 but did not meet significance after a statistical correction for multiple variables, P ≤ .004 (0.05/13). New-onset motion sickness, dizziness as a headache trigger, and orthostatic headaches had P values <.004 and were relatively sensitive and/or specific for the POTS diagnosis. CONCLUSIONS: While no single clinical symptom or headache type reliably establishes the POTS diagnosis, several symptoms can help to distinguish the POTS patient in an adolescent headache population.

Tolerance of a standing tilt table protocol by patients an inpatient stroke unit setting: a pilot study.

BACKGROUND AND PURPOSE: To describe and examine physiologic and self-reported indices of tolerance to a standing tilt table protocol (STTP) among patients following an acute stroke. METHODS: We undertook a prospective, observational pilot study of patients admitted to a stroke unit of a single academic medical center. A clinical protocol for the use of the tilt table was developed and applied to subjects in the acute phase following a stroke. The protocol involved a stepwise process to gradually raise the subject into a standing position on the tilt table platform, at 10° intervals from 60° to 90°. Tolerance of the STTP was operationally defined as the ability to sustain 60° or greater of tilt table inclination for a minimum of 5 minutes, without signs or symptoms of intolerance. Specific measures recorded were frequencies of the highest angle achieved, the duration of standing time tolerated, and physiologic response. RESULTS: Thirty-six patients with ischemic or hemorrhagic stroke (22 women and 14 men) aged 24 to 87 (mean age = 62, SD = 16) years participated in a single trial of the STTP. Fifty-three percent of subjects (N = 19) attained 60° or higher on the tilt table, with a mean total standing time of approximately 9 minutes. DISCUSSION AND CONCLUSIONS: This pilot study suggests that the use of a tilt table is well tolerated among patients in the acute stroke phase and may be an effective tool for introducing early upright mobilization to a medically fragile patient population.Video Abstract available (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A35) for more insights from the authors.

Autonomic dysfunction in patients with orthostatic dizziness: validation of orthostatic grading scale and comparison of Valsalva maneuver and head-up tilt testing results.

OBJECTIVES: To investigate whether the Korean version of the Orthostatic Grading Scale (KOGS) is a reliable and valid measure for evaluating the severity of symptoms of orthostatic intolerance (OI) and to compare the diagnostic accuracy of Valsalva maneuver (VM) and head-up tilt test (HUTT) in identifying sympathetic adrenergic failure (SF). METHODS: A back-translation approach was used to develop the KOGS. One hundred seventy two patients with orthostatic dizziness (OD) as a presenting symptom of OI and 133 healthy controls were enrolled. All patients completed the 5-item, self-report KOGS and 58% (100/172) of patients were randomly selected for a retest with the questionnaire. The degree of the severity of autonomic dysfunction was measured by the composite autonomic severity score (CASS). RESULTS: The incidence of orthostatic hypotension (OH) in HUTT was 21%. The KOGS scores in patients showed good internal consistency (Cronbach's α=0.90) and test-retest reliability (correlation coefficient=0.77 to 0.89). The total and each item scores of KOGS correlated with the degree of the severity of autonomic dysfunction estimated as CASSs in patients. Approximately 70% (116/172) of patients showed at least one abnormality in either HUTT or VM. The incidence (43%) of an abnormal BP response in VM was two times higher than the incidence of OH in HUTT. DISCUSSION: The KOGS is a reliable and valid tool for screening patients with OD. VM is superior to HUTT in detecting SF. Thus, VM and HUTT should be combined to evaluate adrenergic sympathetic function in patients with OD.

Head-up tilt testing for diagnosing vasovagal syncope: a meta-analysis.

BACKGROUND: A systematic evaluation focused on sensitivity and specificity of head-up tilt testing (HUT) for diagnosing vasovagal syncope has not been previously performed. We conducted a meta-analysis of studies comparing HUT outcome between patients with syncope of unknown origin and control subjects without previous syncope. METHODS: We searched Pubmed and Embase databases for all English-only articles concerning case-control studies estimating the diagnostic yield of HUT, and selected 55 articles, published before March 2012, including 4361 patients and 1791 controls. The influence of age, test duration, tilt angle, and nitroglycerine or isoproterenol stimulation on tilt testing outcome was analyzed. RESULTS: Head-up tilt testing demonstrated to have a good overall ability to discriminate between symptomatic patients and asymptomatic controls with an area under the summary receiver-operating characteristics curve of 0.84 and an adjusted diagnostic odds ratio of 12.15 (p<0.001). A significant inverse relationship between sensitivity and specificity of tilt testing for each study was observed (p<0.001). At multivariate analysis, advancing age and a 60° tilt angle showed a significant effect in reducing sensitivity and increasing specificity of the test. Nitroglycerine significantly raised tilt testing sensitivity by maintaining a similar specificity in comparison to isoproterenol. CONCLUSIONS: The results from this meta-analysis show the high overall performance of HUT for diagnosing vasovagal syncope. Our findings provide useful information for evaluating clinical and instrumental parameters together with pharmacological stressors influencing HUT accuracy. This could allow the drawing of tilt testing protocols tailored on the diagnostic needs of each patient with unexplained syncope.

Tilt table testing and implantable loop recorders for syncope.

This article summarizes the major contributions of tilt table tests and implantable loop recorders to the diagnosis of syncope and provides simple recommendations for these tests. Tilt table tests have provided important benefits in the field of neurally mediated syncope. However, they have significant limitations. Implantable loop recorders also are proving very useful. They have identified 2 populations of older patients with syncope who may benefit from permanent pacing. Randomized studies have established the safety and efficacy of their early application in the diagnosis of syncope.

Teste de inclinação (Tilt-test): do necessário ao imprescindível / Tilt test: from the necessary to the indispensable / Test de inclinación (Tilt-test): de lo necesario a lo imprescindible

O teste de inclinação (TI) é muito utilizado para a investigação de síncopes e pré-síncopes, pois possibilita o diagnóstico de diferentes tipos de disautonomias. A principal causa de síncope é a Síndrome Vasovagal, cujo diagnóstico é o mais frequente entre as indicações de TI. O exame é utilizado há cerca de 20 anos, mas muitos médicos desconhecem a metodologia. São importantes a indicação apropriada, após exclusão de causas cardíacas de síncope, e a orientação do paciente para garantir a tranquilidade e a segurança do teste. Existem controvérsias na literatura sobre a capacidade diagnóstica e a confiabilidade dos resultados. Os estudos com protocolos diversos podem explicar a variabilidade dos resultados. Nesta revisão, são colocadas as indicações e a metodologia recomendadas pelas diretrizes, complicações, limitações e perspectivas desse exame.

The head-up tilt test (HUTT) is widely used for investigation of syncope and presyncope, since it allows diagnosing different types of dysautonomia. The main cause of syncope is the vasovagal syndrome, the most common diagnosis among patients with HUTT indication. The test has been used for nearly 20 years, but many doctors are unaware of the methodology. After the cardiac causes of syncope are ruled out, the appropriate indication of the test and instructions to patients are important to ensure that the test will be carried out in a safe and relaxed manner. There are controversies in the literature over the diagnostic capacity and reliability of results. Studies with various protocols may explain the variability of results. This review describes the guidelines-recommended methodology and indications, complications, limitations and perspectives of this test.

El test de inclinación (TI) es muy utilizado para la investigación de síncopes y presíncopes, pues posibilita el diagnóstico de diferentes tipos de disautonomías. La principal causa de síncope es el Síndrome Vasovagal, cuyo diagnóstico es el más frecuente entre las indicaciones de TI. EL examen es utilizado hace cerca de 20 años, pero muchos médicos desconocen la metodología. Son importantes la indicación apropiada, después de exclusión de causas cardíacas de síncope, y la orientación del paciente para garantizar la tranquilidad y la seguridad del test. Existen controversias en la literatura sobre la capacidad diagnóstica y la confiabilidad de los resultados. Los estudios con protocolos diversos pueden explicar la variabilidad de los resultados. En esta revisión, son colocadas las indicaciones y la metodología recomendadas por las directrices, complicaciones, limitaciones y perspectivas de ese examen.

Tilt test--from the necessary to the indispensable.

The head-up tilt test (HUTT) is widely used for investigation of syncope and presyncope, since it allows diagnosing different types of dysautonomia. The main cause of syncope is the vasovagal syndrome, the most common diagnosis among patients with HUTT indication. The test has been used for nearly 20 years, but many doctors are unaware of the methodology. After the cardiac causes of syncope are ruled out, the appropriate indication of the test and instructions to patients are important to ensure that the test will be carried out in a safe and relaxed manner. There are controversies in the literature over the diagnostic capacity and reliability of results. Studies with various protocols may explain the variability of results. This review describes the guidelines-recommended methodology and indications, complications, limitations and perspectives of this test.

Cardiac repolarization variability in patients with postural tachycardia syndrome during graded head-up tilt.

OBJECTIVE: The aim of this study was to assess cardiac ventricular repolarization in patients with postural tachycardia syndrome (POTS) and further the possible link between ventricular repolarization and sympathetic nervous system activity. METHODS: We recorded body surface ECGs together with plasma noradrenaline (NE) spillover, and muscle sympathetic nerve activity (MSNA) in twelve healthy control subjects (CON; 5 males; age: 23±2 yrs) and 13 subjects with postural tachycardia syndrome (POTS; 4 males; 32±13 yrs) during graded head-up tilt (0°-20°-30°-40°). Ventricular repolarization was assessed by computing various measures of beat-to-beat QT interval variability and T wave amplitude. RESULTS: In patients with POTS, baseline heart rates were higher and MSNA increases during tilt were more pronounced than in CON. None of the QT variability measures was significantly affected by tilt or different between CON and POTS when corrected for heart rate. Contrary, the T wave amplitude flattened due to tilt (p<0.001) and this effect was significantly more pronounced in POTS (32% at 40°) than in CON (21% at 40°; p=0.03). CONCLUSIONS: Beat-to-beat variability of the QT interval is normal in patients with POTS. However, significantly more attenuated T waves during head-up tilt together with elevated MSNA levels suggest increased sympathetic outflow to the ventricular myocardium in patients with POTS. SIGNIFICANCE: Monitoring of the T wave during tilt test may provide a non-invasive tool for assessing excessive sympathetic outflow to the ventricular myocardium.

'Front-loaded' head-up tilt table testing: validation of a rapid first line nitrate-provoked tilt protocol for the diagnosis of vasovagal syncope.

Head-up tilt testing is the investigation of choice in the diagnosis of vasovagal syncope. The test is time consuming and labour intensive, with conventional tilt testing taking up to 45 min. We compared a shortened 'front-loaded' 20-min glyceryl trinitrate-provoked head-up tilt (FLGTN-HUT) with the standard 40-min passive tilt (HUT) as first line investigations in patients with unexplained syncope and asymptomatic controls. In the study, 149 consecutive patients with unexplained syncope and 83 asymptomatic controls were enrolled. Subjects were randomly assigned to FLGTN-HUT (800 mcg, metred spray) or HUT, then the opposite tilt-test 1 week later. Seventeen (11.4%) patients had diagnostic haemodynamic changes and symptom reproduction during HUT and 54 (36.2%) during FLGTN-HUT. A total of 24.8% more patients had a positive test with FLGTN-HUT than with passive HUT (95% CI: 16.3%, 33.4%). Nine (10.8%) controls had significant haemodynamic changes during HUT and 23 (27.7%) during GTN provocation. Seven controls had haemodynamic changes on both HUT and FLGTN-HUT testing. The controls group had 16.8% more significant haemodynamic changes with FLGTN-HUT than with HUT (95% CI: 0.06, 27.4). The front-loaded GTN protocol provided a higher diagnostic rate than passive tilt testing, and provides a rapid alternative to conventional methods, though false positivity rates are higher.

Evaluating tilt table testing in syncope 2: management options.

This is a two-part unit on syncope and the value of tilt table testing. Part 1 discussed the physiology of syncope, the procedure of tilt table testing, and indications and contraindications for it. This second part outlines the four common non-cardiac causes of syncope, treatment and management options.