Cerebral oxygenation monitor during head-up and -down tilt using near-infrared spatially resolved spectroscopy

Reflectance near-infrared spectroscopy (NIRS) has become a suitable and easily manageable method to monitor cerebral oxygenation changes in presyncopal and syncopal symptoms caused by postural changing or standing. A new clinical tissue oxygenation monitor has been recently developed which measures absolute tissue haemoglobin saturation (Tissue Oxygenation Index, TOI) utilizing spatially resolved spectroscopy (SRS). The present study examined the effects of postural changes on cerebral oxygenation as reflected in SRS-NIRS findings. Cerebral oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), and the TOI were recorded from both sides of the forehead in five healthy male subjects (age range, 28-40 years) during 90 degrees head-up tilt (HUT) and -6 degrees head-down tilt (HDT). Three series of measurements were carried out on separate days. O2Hb was decreased during HUT. TOI was significantly lower in HUT than in the supine position (SUP). There was no significant change in TOI during HDT. A significant session effect was observed in the left forehead TOI during SUP, but not in the right. SRS-NIRS measurements confirmed sub-clinical alterations of cortical oxygenation during HUT. NIRS data from the left side of the forehead, which may vary with cognitive or emotional activation, were more variable than those from the right side.     

Nitrate‐Potentiated Head‐Up Tilt Testing in Older Patients: Outcomes,Hemodynamic Responses and Prodrome Recognition

Background: To compare head‐up tilt testing (HUT) outcomes and hemodynamic responses, and the prevalence and correlates of prodromes, in elderly and younger patients with suspected vasovagal syncope (VVS). Methods: Consecutive outpatients with a history of recurrent unexplained syncope underwent HUT by being tilted to 70°; the test was potentiated by the administration of 300 μg of nitroglycerine after 20 minutes. Occurrence of VVS and hemodynamic responses during passive and nitroglycerine phases of HUT were evaluated; symptoms preceding HUT‐induced syncope were recorded, together with heart rate and arterial blood pressure values. Results: Four hundred and sixty of the 743 patients were HUT positive: 156 fainted during the unmedicated phase and 304 after nitroglycerine administration. The patients aged ≥65 years (n = 102) experienced VVS more frequently during the pharmacological stage of HUT; the overall rate of positive results was similar to that observed in the patients aged 36–64 years (n = 329) and only slightly lower than that observed in those aged ≤35 years (n = 312). In the older patients, who experienced fewer and mainly prodrome‐free spontaneous syncopal episodes, HUT increased the number of premonitory symptoms, and there were no significant age‐related differences in symptom prevalence or timing or the patients’ hemodynamic characteristics. Conclusions: The rate of VVS induced by nitroglycerine‐potentiated HUT is similar in elderly and younger patients. In the former, nitroglycerine‐potentiated HUT significantly increases the prevalence of prodromes in comparison with spontaneous episodes, which suggests that it may be useful not only for diagnosis but also for patient counseling. (PACE 2010; 33:1210–1216)     

Can stroke volume and cardiac output be determined reliably in a tilt‐table test using the pulse contour method?

The applicability of the finger pressure‐derived pulse contour (PC) technique was evaluated in the measurement of stroke volume (SV), cardiac output (CO) and their changes in different phases of the tilt‐table test. The reference method was whole‐body impedance cardiography (ICG). A total number of 40 physically active patients, aged 41 ± 19 years, were randomly chosen from a pool of 230. Specifically speaking, 20 of the patients experienced (pre)syncope (tilt+ patients) during the head‐up tilt (HUT), and 20 did not (tilt–). A total number of three measurement periods, 30–60 s each, were analysed: supine position, 5 min after the commencement of HUT, and 1 min before set down. SV and CO values measured by PC underestimated significantly those measured by ICG (biases ± SD 19 ± 14 ml and 1·55 ± 1·14 l min^–1, respectively) in agreement with earlier reports. The bias between the methods was almost the same in the different phases of the test. However, the SD of the bias was bigger for tilt+ (P<0·05). When the bias between the methods was eliminated by scaling the first measurement to 100%, the agreement between the methods in the second and third measurements was clearly better than without scaling. Both methods showed a physiological drop in SV after the commencement of HUT. These results indicate that PC suffices in tracking the changes in CO and SV, but for absolute values it is not reliable.     

Is Home Orthostatic Self‐Training Effective in Preventing Neurally Mediated Syncope?

BACKGROUND: Repeated orthostatic stress may prove to be of benefit in the regulation of neurally mediated syncope. But the role of home orthostatic self-training is not established to prevent symptoms in patients with neurally mediated syncope. We performed a prospective and randomized study to evaluate the effectiveness of repeated home orthostatic self-training in preventing tilt-induced neurally mediated syncope. METHODS AND RESULTS: Fourty-two consecutive patients (24 males and 18 females, mean age 39 years, 16-68 years) with recurrent neurally mediated syncope were randomized into the tilt training and control groups. The home orthostatic self-training program consisted of daily sessions for 7 days a week for 4 weeks. In order to determine the effects of home orthostatic self-training, we repeated the head-up tilt test in both groups 4 weeks later. Among the tilt-training group, 9 of 16 patients (56%) had a positive response on follow-up head-up tilt test. Among the untreated control group, 9 of 17 patients (53%) had a positive response on follow-up head-up tilt test. In subgroup analyses according to the number of tilt-training sessions or the classified type, we found no differences in the follow-up head-up tilt test responses. Spontaneous syncope or presyncope over mean follow-up of 16.9 months were observed in 42.9% versus 47.1% in the tilt-training and control group, respectively. CONCLUSIONS: Home orthostatic self-training was ineffective in reducing the positive response rate of head-up tilt test in patients with recurrent neurally mediated syncope.     

Tilt Training: A New Treatment for Recurrent Neurocardiogenic Syncope and Severe Orthostatic Intolerance

Medical treatment of neurocardiogenic syncope is insufficient in many cases. We have observed a therapeutic effect of repeated head-up till testing. Therefore, we have started a program of tilt training for heavily symptomatic patients. After hospital admission, they were tilted daily (60° inclination) until syncope, or until a duration of 45–90 minutes (90 sessions in 13 patients). The mean tilt tolerance, at the first diagnostic head-up tilt table test, was 22.3 minutes (st. dev. 10.9). Before hospital discharge, 12/13 patients could sustain the full duration of tilt table testing without any symptom. In one patient syncope persisted. The patients were instructed to continue a program of daily tilt training at home, by standing against a wall for 30 minutes, one or two times per day. This resulted in a complete disappearance of syncope in all 13 patients.
Orthostatic intolerance and the excessive autonomic reflex activity of neurocardiogenic syncope can be remedied by a program of continued tilt training, without the administration of drugs.     

Comparison of a Shortened Isosorbide Dinitrate-Potentiated Head-Up Tilt Testing with the Conventional Protocol: Tolerance and Diagnostic Accuracy

Background: The head-up tilt test (HUT) is widely used to investigate unexplained syncope; however, in clinical practice, it is long and sometimes not well tolerated. Objectives: To compare the sensitivity, specificity, accuracy, and patients' tolerance of a conventional and shortened HUT. Methods: Patients with a history of vasovagal syndrome (VVS) were randomized to a conventional HUT (group I) consisting of 20-minute passive tilt followed by 25 minutes after administration of sublingual isosorbide dinitrate (ISDN), or a shortened HUT (group II) where ISDN was given immediately after tilt and observed for 25 minutes. The control group consisted of age- and gender-matched subjects without VVS symptoms. A specific questionnaire to evaluate tolerance was applied. Results: Sixty patients (29 ± 10 years, 82% female) were included. In group I, 22/30 patients had a positive HUT compared to 21/30 in group II (73% vs 70%, P = 0.77). There was also no difference in the accuracy between the two protocols (63% vs 73%, P = 0.24). The time to positivity was shorter in group II (13.2 minutes vs 30 minutes, P < 0.001). Within the control group (n = 60), the frequency of false-positives was 47% and 23% for the conventional and shortened HUT, respectively (P = 0.058). After conventional HUT, 65.2% subjects reported that the test was too long compared to 25% subjects after the shortened HUT (P = 0.002). Conclusion: In this study, the HUT without passive phase was not inferior to the conventional HUT regarding sensitivity, specificity, and accuracy. Furthermore, the shortened ISDN-potentiated protocol allowed faster diagnosis and was better tolerated. (PACE 2012; 35:1005-1011).     

Cardiovascular effects of ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel

The objective of this randomized, double-masked, cross-over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel. Twenty-four young healthy subjects received for 2 weeks either twice daily 0.5% timolol solution or once daily 0.1% timolol hydrogel. Heart rate (HR), blood pressure, atrio-ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head-up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0.5% aqueous solution than after 0.1% hydrogel. A 0.5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head-up tilted position while no significant effects were observed with 0.1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean +/- SD, 77 +/- 11 bpm versus 86 +/- 13 bpm, P < 0.05). Timolol aqueous solution slightly decreased QTc during tilt (5.9 +/- 5.6 ms, P < 0.01). During tilt tests, timolol aqueous solution slightly increased atrio-ventricular conduction (7.2 ms, P = 0.02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0.5% timolol aqueous solution produces more pronounced cardiac beta-blocking effects than 0.1% timolol hydrogel.     

Usefulness of orthostatic self-training for the prevention of neurocardiogenic syncope

To clarify the effectiveness of an orthostatic self-training program for the prevention of neurocardiogenic syncope, twenty-four consecutive head-up tilt induced syncopal patients (12 men, 12 women; mean age 34 +/- 20 years) were treated with an orthostatic self-training program. The syncope was induced by head-up tilt testing (+ 80 degrees for 30 minutes) with or without the use of isoproterenol in all patients reproducibly. The hemodynamics during the syncope were of the cardioinhibitory type in 4, vasodepressor type in 7, and mixed type in 13 patients. The onset time of the tilt induced syncope was 16 +/- 10 minutes after the upright position. The orthostatic self-training included standing against a wall without moving twice a day every day for a planned duration of up to 30 minutes at home. The head-up tilt response was reevaluated with the same protocol as the initial study after 22 +/- 6 days based on the patient's daily recording of the self-training, and the clinical effect of the training program performed only once a day at home was noted over a mean follow-up of 9.5 +/- 3.4 months (range 5-18 months). Tilt induced syncope after the self-training was observed in 2 of 24 patients. However, spontaneous syncope was not observed in any of the patients during follow-up. In conclusion, orthostatic self-training significantly improved the symptoms in patients with neurocardiogenic syncope. Once a day training for up to 30 minutes was effective and easily accepted by the patients for the prevention of neurocardiogenic syncope.     

直立倾斜试验诊断血管迷走性晕厥的价值

目的研究直立倾斜试验（ＨＵＴ）诊断血管迷走性晕厥的价值。方法６７例原因不明的晕厥患者、２０例正常对照组行ＨＵＴ时,并采用特异性及敏感性较高的静滴异丙肾上腺素重复试验。观察心率、收缩压、舒张压变化。结果４３例阳性患者中,血管抑制性晕厥３１例（３１／６７）,混合性晕厥１２例。患者组,基础早搏时与阳性时的心率、收缩压、舒张压之间有高度显著性差异（Ｐ＜０００１）。静滴异丙肾上腺素敏感性６４％,特异性８５％。结论静滴异丙肾上腺素重复倾斜试验对诊断血管迷走性晕厥具有重要价值。     

Diagnostic value of nitrate stimulated tilt testing without preceding passive tilt in patients with suspected vasovagal syncope and a healthy control group

BACKGROUND: The contribution of the passive tilt phase, in a combined nitrate stimulated tilt protocol may be low yielding. In order to develop a shortened, and thus easier to perform test, we investigated the optimal duration of a nitrate tilt protocol without a preceding passive phase. METHODS: Thirty-eight consecutive patients (18F/20M; mean age 46 +/- 16) with clinically suspected vasovagal syncope and 31 control subjects (15F/16M; mean age 40 +/- 18) were tested. The subjects were tilted to 70 degrees for a maximum period of 30 minutes, and sublingual nitroglycerin 0.4 mg spray was administrated directly after attaining erect posture. Receiver operator characteristics (ROC) analysis was done to determine the optimal test duration. RESULTS: In the patient group 31 (82%) and in controls 5 (16%) had a positive test. Sensitivity, specificity, and accuracy at test end were 82, 84, and 83%, respectively. ROC analysis revealed that a maximum accuracy of 83% was attained at 14 minutes, with a sensitivity and specificity of 79 and 87%, respectively. CONCLUSION: Nitrate stimulated tilt testing, without a preceding passive tilt phase, and limited to a test duration of 15 minutes, provides an accurate, sensitive, and specific method to provoke vasovagal reactions in subjects with clinically suspected vasovagal syncope.     

Low Body Mass Index Is Associated with a Positive Response during a Head‐Up Tilt Test

Background : To describe the association between body mass index (BMI) and a positive response during a head‐up tilt test (HUT) in patients referred for an investigation of syncope. Methods : Observational study of patients referred for the diagnostic evaluation of syncope. Patients were divided into four groups according to their BMI: <18.5 kg/m², 18.5–24.9 kg/m², 25–29.9 kg/m², and > 30 kg/m². Results : A total of 419 patients were evaluated. The mean age was 43 ± 22 years, and 62% were female. The prevalence of a positive tilt test was different between groups when stratified by BMI (P = 0.01), with a higher proportion of patients with positive tests among those with BMI <18.5 kg/m² compared with other groups (P = 0.05). Multivariate analysis also showed that underweight patients had a 3.9 times higher risk for a positive HUT response (P = 0.01); additionally, the use of contraceptive drugs was associated with a protective effect during HUT (odds ratio: 0.35, confidence interval:0.19–0.45, P = 0.001). Conclusion : In our sample, changes in BMI are associated with a positive response for HUT, and oral contraceptives seemed to protect against this response. Further studies are needed with larger numbers of patients to corroborate this finding. (PACE 2013; 36:37–41)     

Metabolic syndrome is associated with decreased heart rate variability in a sex‐dependent manner: a comparison between 252 men and 249 women

Impaired heart rate variability (HRV) is associated with increased risk of cardiovascular disease, but evidence regarding alterations of HRV in metabolic syndrome (MetS) remains elusive. In order to examine HRV in MetS, we subjected 501 volunteers without atherosclerosis, diabetes or antihypertensive medication, mean age 48 years, to passive head‐up tilt. The subjects were divided to control men (n = 131), men with MetS (n = 121), control women (n = 191) and women with MetS (n = 58) according to the criteria by Alberti et al. (Circulation, 2009, 120, 1640). In unadjusted analyses (i) men and women with MetS had lower total power and high‐frequency (HF) power of HRV than controls whether supine or upright (P<0·05 for all). (ii) Supine low‐frequency (LF) power of HRV was lower in men (P = 0·012) but not in women (P = 0·064) with MetS than in controls, while men and women with MetS had lower upright LF power of HRV than controls (P <0·01 for both). (iii) The LF:HF ratio did not differ between subjects with and without MetS. After adjustment for age, smoking habits, alcohol intake, height, heart rate and breathing frequency, only the differences in upright total power and HF power of HRV between women with MetS and control women remained significant (P<0·05). In conclusion, reduced total and HF power of HRV in the upright position may partially explain why the relative increase in cardiovascular risk associated with MetS is greater in women than in men. Additionally, the present results emphasize that the confounding factors must be carefully taken into consideration when evaluating HRV.     

Characterization of the Factors that Determine the Effect of Sympathetic Stimulation on Heart Rate Variability

Heart rate variability analysis has been used to derive indices of sympathetic tone. As different sympathetic stimuli may give rise to divergent changes in heart rate variability, this study was designed to characterize the factors responsible for these divergent responses. Twelve healthy subjects (7 males, age 24.8 ±3.1 years) were evaluated. Five-minute electrocardiographic recordings were obtained at baseline, following upright tilt, and during isoproterenol infusion (25 ng/kg per min) under control conditions and following parasympathetic blockade. Data were acquired during spontaneous respiration and when breathing was timed with a metronome (15 breaths/min). Under control conditions, both upright tilt and isoproterenol infusion resulted in significant decreases in the SD and MSSD from baseline values of 69 ± 3 ms and 64 ± 5 ms to 48 ± 4 ms and 21 ± 5 ms during tilt and 44 ± 4 ms and 20 ± 5 ms during isoproterenol infusion, respectively. LF power also significantly increased from 0.47 ±0.17 In (beats/min)² at baseline to 1.90 ± 0.20. In (beats/min)² and 1.34 ± 0.18. In (beats/min)² during tilt and isoproterenoi infusion, respectively. No change in HF power was noted. Following parasympathetic blockade, all heart rate variability parameters were significantly decreased. No significant change from baseline in the SD, MSSD, or HF power was noted with either tilt or isoproterenol infusion. The LF power increased only with tilt from a baseline value of -3.17 ± 0.17 in (beats/min)² to -0.41 ± 0.19 in (beats/min)². Similar changes were noted during spontaneous respiration and metronome breathing. These findings demonstrate that the response of the sinus node to β–adrenergic stimulation depends on the mode of stimulation. In addition, the associated level of parasympathetic tone affects the observed changes in heart rate variability that are associated with sympathetic stimulation.     

The Use of Head-Upright Tilt Table Testing in the Evaluation and Management of Syncope in Children and Adolescents

Recurrent syncope in an otherwise healthy child or adolescent is a common anxiety provoking disorder. Vasovagally mediated hypotension and bradycardia are believed common, yet difficult to diagnose, causes of syncope in this age group. Upright tilt table testing has been suggested as a potential method to test for vasovagal episodes. This study evaluated the utility of this technique in the evaluation and management of recurrent syncope in children and adolescents. Thirty patients with recurrent unexplained syncope were evaluated by use of an upright tilt table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/min given intravenously), in an attempt to produce hypotension, bradycardia, or both. There were 15 males and 15 females, mean age 14 +/- 6 years. Each of the tilt positive patients received therapy with either fluorohydrocortisone, beta blockers, or transdermal scopolamine. Syncope occurred in six patients (20%) during the base line tilt and in 15 patients (50%) during isoproterenol infusion (total positives 70%). All initially positive patients were rendered tilt negative by therapy. Over a mean follow-up period of 20 months, no further episodes have occurred. We conclude that tilt table testing is a useful and effective test in the evaluation of unexplained syncope in childhood.     

Reproducibility of Head Upright Tilt Table Test Results in Patients with Syncope

Head upright tilt table testing is a promising technique for the evaluation and management of vasovagal (neuroregulatory) syncope. In order to determine the day-to-day reproducibility of results using this technique we performed head upright tilt table testing (with or without graded isoproterenol infusion) in 21 patients (12 males, 9 females, mean age 34 ± 19.1 years). During the first tilt study a total of 14 patients experienced syncope (six during baseline tilt, mean tilt time 15.8 ± 7 minutes, eight following tilt with graded isoproterenol infusion, mean tilt time 17.7 ± 9 minutes) while seven were negative. During the second tilt study (performed 3–7 days following the first study) the results of the first study were duplicated in 19 patients (90%) (six during baseline tilt, mean time 17.5 ± 8 minutes, eight following graded isoproterenol infusion, mean time 15.9 ± 7 minutes), however the level of provocation required to provoke syncope differed from that needed in the initial test in five patients (24%). We conclude that the results of head upright tilt table testing with graded isoproterenol infusions can be duplicated in 90% of patients, although some day-to-day variability exists in the degree of provocation necessary to elicit a positive response.