Prolonged Asystole During Head-Up Tilt Table Testing After Beta Blockade

Neurally mediated vasodepressor syncope is a common clinical problem. The diagnosis is generally associated with a benign prognosis, however, a less common "malignant" form has been identified. Head-up tilt table testing is helpful in the confirmation of the diagnosis of neurally mediated vasodepressor syncope and may be useful in the selection of therapy. One form of therapy commonly used is beta blockade. In this case report we describe a patient with neurally mediated vasodepressor syncope who developed asystole during head-up tilt table testing after treatment with a beta blocker.     

Tilt Table Testing: Concepts and Limitations

Recurrent unexplained syncope is a common and often frustrating clinical problem. Over the last decade, bead upright tilt table testing bas emerged as an important diagnostic metbod far the identification of individuals whose syncope is likely to be neurocardiogenic in origin. At the same time, tilt table testing, by providing syncopal episodes in a controlled setting, has allowed for a much greater understanding of these disorders. This article reviews the concepts behind tilt table testing, as well as the uses and limitations of the evolving diagnostic modality.     

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.     

Low Dose Disopyramide Often Fails to Prevent Neurogenic Syncope During Head-Up Tilt Testing

Low dose disopyramide has been used to prevent neurally-mediated syncope during head-up tilt testing but a correlation between blood levels and efficacy has not been described. We measured disopyramide levels in 15 patients with recurrent syncope and positive 70° head-up tilt tests who underwent one or more repeat tests on the drug. There were 9 males and 6 females, age range 15–78 years. Fourteen of the 15 patients had structurally normal hearts. The daily disopyramide dose was 645 ± 165 mg (mean ± SD). Patients developed syncope during 9 tests and had no syncope during 12 tests. The mean disopyramide level in patients with positive tests was significantly lower than the level in patients with negative tests (2.4 ± 0.15 μ/mL vs 3.2 ± 0.22 μ/mL, P = 0.018). Six patients were tested twice on different disopyramide doses. Five of these six patients had syncope during head-up tilt testing on the lower dose and negative tests on the higher dose (disopyramide levels 2.2 μ 0.17 μ/mL vs 3.2 μ0.17 fi/mL, P = 0.004). Thus, disopyramide is effective in preventing neurogenic syncope during head-up tilt testing, but higher blood levels are often necessary for efficacy. In a given patient, failure to respond to low dose disopyramide does not preclude success on higher doses.     

The Usefulness of Head-Up Tilt Testing and Hemodynamic Investigations in the Workup of Syncope of Unknown Origin

To enhance the clinical evaluation of patients suffering from recurrent syncope of unknown origin, the integrity of mechanisms controlling blood pressure was examined in 151 patients utilizing a screening tilt test. Ninety-eight patients had an abnormal blood pressure and/or heart rate response to tilt testing, including provoked syncopal attacks in 63 patients. Whenever indicated, the screening tilt test was followed by blood volume and hemodynamic determinations, as well as autonomic nervous system testing to identify contributing pathophysiological abnormalities (hypovolemia, venous pooling, autonomic dysfunction). Detailed analysis of this battery of tests allowed us to conclude that: (1) The tilt test is commonly a provocative tool in the workup of patients with recurrent syncope due to vasovagal - vasodepressor reactions and other abnormalities of blood pressure regulation; (2) Its usefulness is augmented by associated hemodynamic and blood volume evaluations; (3) The identification of contributory pathophysiological mechanisms of blood pressure control facilitates specific therapeutic interventions.     

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.     

Polymorphic Ventricular Tachycardia Induced During Tilt Table Testing in a Patient with Syncope and Probable Dysfunction of the Sinus Node

We present a case of life-threatening arrhythmia occurring during tilt table testing in a 44-year-old man with syncope. Polymorphic ventricular tachycardia occurred while the patient was tilted up under the intravenous infusion of isoproterenol (2 μg/min). No ischemia, QTc prolongation, or electrolyte abnormality preceded this event. The arrhythmia was not induced by programmed ventricular stimulation or exercise testing. Based on electrophysiological and clinical data, the diagnosis of sick sinus syndrome was entertained.     

Tilt Training: A Treatment for Malignant and Recurrent Neurocardiogenic Syncope

The treatment of neurocardiogenic syncope is insufficient in many cases. We hypothesized that the repeated exposure of the cardiovascular system to orthostatic stress could have a therapeutic effect on the regulation of cardiovascular reflex mechanisms. We have started a program of tilt training for heavily symptomatic patients. After hospital admission, patients were tilted daily (60-degree inclination), until syncope, or until a maximum of 45–90 minutes. The patients were instructed to continue a program of daily tilt training at home: two 30-minute sessions of upright standing against a vertical wall. No medication was prescribed. A total of 260 tilt table sessions were performed in 42 patients. The first tilt test was positive after 21 ± 13 minutes. The syncope was cardioinhibitory in 14 cases, vasodepressor in 19, mixed in 9. At the time of hospital discharge, 41 patients could support 45 minutes of head-up tilting. After a mean follow-up time of 15.1 (SD 7.8) months, 36 patients remained completely free of syncope. Syncope still occurred in one patient and presyncope in four patients. One patient died from an extensive myocardial infarction. The abnormal autonomic reflex activity of neurocardiogenic syncope can be remedied by a program of continued tilt training without the administration of drugs. This new treatment has proven to be effective for the vasodepressor and the cardioinhibitory type of syncope.     

Syncope: The Diagnostic Value of Head-Up Tilt Testing

To determine the usefulness of prolonged head-up tilt in the diagnosis of neurally mediated syncope, 201 patients with history of syncope of unknown cause and 102 age and gender matched control subjects underwent a 40 minute 60 degree head-up tilt test. Head-up tilt elicited syncope (i.e., was positive) in 74 of the 201 patients (37%) with a history of unexplained syncope and in only 6 of the 102 controls (6%). The specificity of the test was 100% in patients 60 years of age and older. Symptoms during tilt-induced syncope were identified by the patients as similar to those they had suffered during their spontaneous episodes. All 80 subjects who had tilt-induced syncope recovered without sequelae. The positive predictive value of a positive response to head-up tilt was 93% and the negative predictive value was 43%. The results indicate that the prolonged head-up tilt test is a very specific procedure of high diagnostic value in patients with a history of unexplained syncope. It is particularly useful in the elderly age groups who have a high incidence of syncope.     

A "Dysautonomic" Head-Up Tilt Test Pattern in Elderly Patients with Neurocardiogenic Syncope

The characteristics of neurocardiogenic syncope (NCS) in elderly patients remain unclear. We compared the hemodynamic profiles of young and older patients with consecutive and positive head-up tilt tests (HUT). Continuous, noninvasive, and reliable monitoring of arterial pressure (AP) and heart rate (HR) was done throughout 46 consecutive positive HUTs of symptomatic patients. The population (12-82 years old) was divided into two groups: younger patients, Y (n = 25, < or = 65 years), and older patients, O (n = 21). Changes in AP and HR after the first minute of tilting, during the stable orthostatic phase and during syncope were compared. Except for systolic pressure, baseline hemodynamic parameters were similar in Y and O. No difference appeared in the mean time elapsed before syncope (19+/-9 vs 22+/-2 min). Asymptomatic hypotension was observed, only in O, 1 minute after tilting, followed by a progressive fall in the mean AP before syncope (0+/-0.9 vs -1+/-0.7 mmHg/min) without HR increase (0.7+/-1 vs 0+/-0.6 beats/min). This pressure slope was strongly related to age (r = 0.54, P < 0.001). Hemodynamic recording during HUT identifies a dysautonomic pattern in elderly patients with NCS and the abnormal AP/HR responses to orthostasis may be a feature specific to this population. Although the central mechanism of NCS is common to all ages, the age-related characteristics of the trigger event may indicate the need for specific management at different ages.     

Tilt Table Testing of Young Adult Patients: Improved Speed and Sensitivity Using an Isoproterenol Bolus and a Continuous 60° Tilt

The tilt table is a diagnostic device used to induce vagal syncope and determine etiology. Sensitivity enhancing techniques, such as the administration of isoproterenol, can be applied to children and young adults to compensate for the otherwise low sensitivity (20%-30%) observed in that population. This study describes an improved test that offers a simplified approach while decreasing the amount of time involved by up to 50%, without compromising sensitivity. This 45-minute procedure relies on sensitization with isoproterenol administered as a 2- to 8-μg bolus instead of a continuous infusion. The isoproterenol is injected at the 30th minute of a 45-minute 60° tilt test without returning the patient to the supine position. In this study, the isoproterenol bolus tilt test was found to be "positive" in 24 of 30 patients reporting unexplained syncope: 10 cases before the 30th minute (11.2 ± 8.4 min) and 14 cases after administration of 5.1 ± 1,9 μg of isoproterenol.     

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.     

Plasma Catecholamines and Cyclic AMP Response During Head-Up Tilt Test in Patients with Neurocardiogenic (Vasodepressor) Syncope

To examine hemodynamic, plasma Catecholamines, and cyclic AMP changes during tilt in patients with neurocardiogenic (vasodepressor) syncope, six patients underwent 80± head-up tilt test for 10 minutes with isoproterenol infusion (1–3 μg/min). Venous blood was sampled in the supine position, at 3 minutes of tilt, and at the onset of vasodepressor reaction during tilt. AH patients had previous tilt studies in which vasodepressor syncope had been induced reproducibly (mean 3.3 episodes in each patient). Syncope was induced at 6.1 ± 0.4 minutes of tilt with an infusion of isoproterenol (mean 1.7 ± 0.3 fig/min). Although arterial pressure and heart rate did not change significantly between in the supine position and at 3 minutes of tilt, plasma norepinephrine increased significantly at 3 minutes of tilt (0.44 ± 0.10 ng/mL; P < 0.05) and at the onset of vasodepressor reaction (0.49 ± 0.12 ng/mL; P < 0.01) compared to the supine position with isoproterenol (0.34 ±0.10 ng/mL). Also, cyclic AMP (cAMP) increased significantly at 3 minutes of tilt (25.3 ± 2.0 pmol/mL; P < 0.005) and at the onset of vasodepressor reaction (29.6 ±1.7 pmol/mL; P < 0.005) compared to the supine position with isoproterenol (20.4 ±1.9 pmol/mL). After administration of selective beta₁-blocker, metoprolol (40 mg/day), plasma norepinephrine, and cAMP during tilt did not change significantly compared to baseline tilt. However, metoprolol prevented the syncope in 3 of 6 patients. After administration of beta₁-, beta₂- blocker, propranolol (30 mg/day), cAMP at 3 minutes of tilt decreased significantly compared to the baseline tilt (16.9 ±1.4 pmol/mL vs 25.3 ± 2.0 pmol/mL; P < 0.05) and propranolol prevented the syncope in all six patients. We concluded that the increase of cAMP may play an important role for the induction of vasodepressor reaction in patients with neurocardiogenic (vasodepressor) syncope. The concentration ofcAMP showed more sensitive response to vasodepressor reaction than that of norepinephrine.     

Asymptomatic Brugada Syndrome Associated with Postural Orthostatic Tachycardia Syndrome:

Autonomic imbalance may work as a modifying factor for initiating lethal arrhythmia in patients with Brugada syndrome. A 26-year-old man with episodes of near syncope was given a diagnosis of an autonomic disorder, postural orthostatic tachycardia syndrome (POTS). The patient spontaneously showed typical Brugada-type ECG, and ventricular fibrillation was induced by programmed electrical stimulation, which allowed the further diagnosis of Brugada syndrome. Although it seems that Brugada syndrome is asymptomatic, its uncommon association of POTS may increase the risk for future arrhythmic events in this patient.     

Demonstration of Syncope in Patients After Pacemaker Implantation: Role of Head-Up Tilt Test to Distinguish Neurocardiogenic Vasodepressor Syncope From Pacemaker Syndrome

It is important to distinguish clinically neurocardiogenic syncope from pacemaker syndrome in patients after pacemaker implantation. We report two syncopal patients with AV sequential physiological pacemakers who displayed neurocardiogenic Vasodepressor syncope (VDS) during head-up tilt (HUT) testing. Neurocardiogenic VDS, as a cause of syncope in patients following pacemaker implantation, might be involved in these patients as well as pacemaker syndrome. HUT is a useful diagnostic test in distinguishing neurocardiogenic VDS from pacemaker syndrome in patients with syncope following pacemaker implantation. Careful evaluations for diagnosis of pacemaker syndrome are needed in these patients.     

Methods Other Than Tilt Testing for Diagnosing Neurocardiogenic (Neurally Mediated) Syncope

The recording of spontaneous episodes of bradycardic neurocardiogenic syncope (NCS) has shown that: a prolonged ventricular asystole seems necessary to cause syncope; asystole is preceded by other bradyarrhythmias in the vast majority of cases; some warning symptoms precede the loss of consciousness in most cases; conventional dual-chamber pacing is efficacious both in patients with a positive response to carotid sinus massage (CSM) and eyeball compression test (EBC) and in those with a positive response to tilt-testing (TT). CSM, EBC, and TT are established tools for diagnosing NCS, when the recording of spontaneous syncope is lacking. When combined together, they are probably able to correctly identify most patients affected by NCS. Nevertheless, whether the type of reflex induced by the cardiovascular reflexivity maneuvers correlates with that of the spontaneous syncope is largely unknown. Our knowledge suggests that the correlation may be unsatisfactory, owing to the following: the variability of the mechanism of spontaneous syncope from patient to patient and also, in the same patient, from one episode to another; the discordance of the type of response when 2 or 3 tests are positive in the same patient, the response being more frequently asystolic with CSM and EBC and more frequently vasodepressor with TT; the different timing between hypotension induced by CSM (in which it follows the bradycardia) and that induced by TT (in which it usually precedes the bradycardia) and the uncertainty about the timing of hypotension during the spontaneous syncope; the good reproducibility of the spontaneous event by CSM and EBC, but not by TT, when cardiac asystole is the manifestation of NCS: and the fairly high rate of false-positive results of cardiovascular reflexivity maneuvers. Hypotension is the main reason for the failure of pacemaker therapy in all the forms of neurocardiogenic syncope (NCS), whether diagnosed by CSM, EBC, or TT. Thus, the need arises to correctly identify the magnitude of the hypotensive reflexes of spontaneous events.     

Postural Orthostatic Tachycardia Syndrome: A Rare Complication Following Electrical Injury

We report on two previously healthy patients who developed severe form of postural orthostatic tachycardia syndrome (POTS) following an electric injury. Both the patients developed symptoms of orthostatic intolerance in the form of dizziness, fatigue, lightheadedness, and palpitations, weeks to months after electrical injury. Orthostatic intolerance produced considerable functional impairment in these patients. Early recognition of POTS when it occurs after an electrical injury allows for prompt evaluation and management to occur. (PACE 2010; 33:e59–e61)     

The Use of Methylphenidate in the Treatment of Refractory Neurocardiogenic Syncope

Recurrent neurocardiogenically mediated episodes of hypotension and bradycardia are a common cause of recurrent syncope that can be identified by head upright tilt table testing. While the use of β-blockers, theophylline, fludrocortisone, disopyramide, and serotonin re-uptake inhibitors can be helpful in preventing further episodes, some patients are unresponsive to or poorly tolerant of these agents. We investigated the use of the central nervous system stimulant and peripheral vasoconstrictor methylphenidate in preventing both tilt induced and spontaneous neurocardiogenic syncope. Seven patients (all women, mean age 31 ± 15 years) with recurrent syncope and positive head upright tilt induced hypotension/bradycardia (refractory to normal therapy) were placed on methylphenidate 10 mg orally three times per day. Six of the seven patients became both tilt negative and clinically asymptomatic over a 7-month follow-up period. We conclude that methylphenidate may be an effective therapy in patients with recurrent neurocardiogenic syncope refractory to other forms of therapy.     

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).