Home Orthostatic Self-Training in Neurocardiogenic Syncope

We assessed the efficacy of daily sessions of home orthostatic self-training (30 minutes per session standing against the wall without moving) in the prevention of neurocardiogenic syncope in 37 patients. Of these, 10 patients were instructed to perform two sessions per day, 14 were instructed to perform a single session per day, and the remaining 13 were instructed to perform one session every other day. The patients who performed one to two sessions of training per day continued to do so over a 6-month follow-up period, during that time none of them experienced spontaneous syncope. Only 5 of 13 patients who were instructed to train once every two days were able to continue doing so over the 6-month follow-up period; however, no spontaneous syncope was observed in these five patients. The remaining 8 of 13 patients could not continue their home training, and syncope or presyncope recurred in three of them during follow-up. We conclude that one session per day of home orthostatic self-training should be prescribed for the prevention of neurocardiogenic syncope.     

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.     

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.     

Neural Monitoring of Vasovagal Syncope

Head-up tilt testing has become a valuable and widely accepted diagnostic tool for evaluation of patients with vasovagal syncope. This test has afforded clinical researchers the opportunity to focus on the hemodynamic, humoral, and neural changes that accompany syncope. We review the animal and clinical studies that provide insight into the possible pathophysiological mechanisms involved in vasovagal syncope. Hemodynamic measurements in patients with vasovagal syncope suggest that a relative decrease in ventricular size and increase in cardiac contractility may be seen in many patients with vasovagal syncope. Patients with vasovagal syncope have also demonstrated numerous "exaggerated" neurohumoral responses to syncope. Differential changes in plasma levels of epinephrine, renin, endothelin, vasopressin, cortisol, prolactin, beta endorphins, and substance P have been reported by some investigators either prior to or during a syncopal episode in patients with vasovagal syncope. The precise pathophysiological significance of these measurements is unknown at the present time. Measurements of autonomic tone may be accomplished indirectly with analysis of heart rate variability or baroreflex slope, or directly by sympathetic neural recordings of the peroneal nerve. We have demonstrated decreased baroreflex slopes in patients with vasovagal syncope. Using microneurography, we and others have demonstrated decreased sympathetic nerve activity occurring 11 ± 3 seconds prior to syncope during bead-up tilt table testing. A variety of other abnormal reflexes, including blunted forearm blood flow responses during exercise, have been demonstrated by others. These observations suggest that pacing instituted after the event may not be as helpful as the use of a hemodynamic sensor that will result in the initiation of pacing prior to sympathetic withdrawal or modify the decrease in sympathetic tone that occurs prior to syncope.     

Predictors of Positive Head-Up Tilt Test in Patients with Suspected Neurocardiogenic Syncope or Presyncope

OH, J.H., et al .: Predictors of Positive Head-Up Tilt Test in Patients with Suspected Neurocardiogenic Syncope or Presyncope. Neurocardiogenic syncope is the most common cause of syncope in patients who present in outpatient clinics. Head-up tilt test (HUT) has been widely used to diagnose neurocardiogenic syncope. However, the HUT does not always produce a positive response in patients with suspected neurocardiogenic syncope. The aim of the present study was to assess the clinical history and characteristics of patients with suspected neurocardiogenic syncope or presyncope who undertook HUT, and to identify prognostic factors of a positive HUT response. During the first phase of HUT, patients were tilted to a 70-degree angle for 30 minutes. If the first phase produced a negative response, the second phase was subsequently performed involving intravenous isoproterenol administration. Of 711 patients, 423 (59.5%) patients showed a positive HUT response. In contrast to previous studies, this study showed that the vasodepressive type (76.6%) was the most common pattern of positive response, and that the rate of positive response during the first phase was low (7.1%). By multivariate analysis, the occurrence of junctional rhythm was found to be a predictor of an impending positive response in HUT   (P < 0.001)   . The shorter time interval between the last episode and HUT was also a predictor of positive response   (P = 0.0015)   . Younger age   (P = 0.0003)   and a history of physical injury during a syncopal episode   (P = 0.019)   were found to be associated with a positive response in the first phase of HUT. (PACE 2003; 26[Pt. I]:593–598)     

Beneficial Effects of Dextro-Amphetamine in the Treatment of Vasodepressor Syncope

Three patients with history of documented hypolension, near syncope, or syncope before or after the administration of isoproterenol during head-up tilt table are reported. Severe bradycardia was also noted in one patient. All three patients responded to the administration of 2.5 mg of oral dextro-amphetamine 45 minutes prior to a repeat head-up tilt table study. The potent central and peripheral adrenergic agonist pharmacological properties of this drug permitted the prevention of severe vasodepressor syncope in these patients.     

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.     

Treatment of Malignant Neurocardiogenic Vasovagal Syncope with a Rate Drop Algorithm in Dual Chamber Cardiac Pacing

A 29-year-old man with malignant vasovagal syncope presented with episodes of abrupt loss of consciousness associated with an aura, totaling more than 10 episodes over 3 months. Holter monitoring showed cardiac arrest with a duration of 15 seconds. Oral propranolol and disopyramide therapy failed to prevent the syncope. A dual chamber pacemaker with a rate drop response algorithm successfully prevented the syncope but not the aura. There may be multifactors involved in the mechanism of this syndrome. The patient has returned to a normal active life. This rate drop algorithm is an effective therapy for the prevention of syncope in malignant vasovagal 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 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.     

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.     

Head-Up Tilt Test in Patients with High Pretest Likelihood of Neurally Mediated Syncope: An Approximation to the "Real Sensitivity" of this Testing

This study was designed to examine the "true sensitivity" of a specific head-up tilt (HUT) testing protocol using clinical findings. The HUT protocol used 45 minutes at 60 degrees for the baseline portion and intermittent boluses of 2, 4, and 6 micrograms of isoproterenol in the second phase. Eighty-eight patients (40 men and 48 women; mean age of 33.8 +/- 16 years) with recurrent syncope and high pretest likelihood of neurally mediated syncope were included. The following were considerated as high pretest likelihood criteria: (1) at least two syncopal episodes; (2) no structural heart disease and normal baseline ECG; (3) age < 65 years; (4) a typical history of neurally mediated syncope, triggering factors plus premonitory signs; and (5) short duration of symptoms and fast recovery without neurological sequelae. Fifty-four patients (61%) had a positive tilt test (34/88 baseline [39%] and 20/50 with isoproterenol [40%]). The shorter time interval between the last syncopal episode and baseline HUT test was the only predictor for a positive response (P < 0.003). Conversely, this time interval was not predictor of positive responses during isoproterenol-tilt testing. In conclusion: (1) we claim a "sensitivity" for this combined protocol of 61%; and (2) our results indicate that patients with syncope of unknown origin must be tilted nearest as possible to the last syncope to increase the positive responses of HUT test.     

Heart Rate Variability During Head-up Tilt Testing in Patients with Suspected Neurally Mediated Syncope

The relation between heart rate variability (HRV) and outcome of head-up tilt testing (HUT) in patients with neurally mediated syncope (NMS) was studied in 30 patients with presumed NMS (33 ± 13 years) and in 11 age-matched controls. After 15 minutes of baseline supine observation, patients were tilted to 60± for 45 minutes or until syncope occurred. HRV parameters included RR intervals, standard deviation of normal-to-normal RR intervals (SDNN), and root mean square successive differences (RMSSD). HRV analysis was performed during 5-minute intervals in the supine position immediately after onset of HUT and before syncope or after 30–35 minutes of tilt in patients without syncope. Syncope occurred after a mean tilt duration of 32 minutes in 14 (47%) of 30 patients with presumed NMS, whereas all controls had an uneventful HUT. In the supine position, RR intervals and RMSSD were comparable among HUT-positive patients, HUT-negative patients, and controls (RR intervals: 799 ± 92, 854 ± 137, and 818 ± 128 ms, P = NS; RMSSD: 43 ± 40, 36 ± 34, and 53 ± 42 ms, P = NS). Baseline SDNN was also comparable in HUT-positive patients versus HUT-negative patients with presumed NMS (50 ± 26 vs 52 ± 20 ms, P = NS). Within 5 minutes preceding syncope or after 30–35 minutes of tilt, RR intervals and RMSSD were shorter in HUT-positive patients compared to HUT-negative patients, or to controls (RR intervals: 606 ± 86 vs 710 ± 117 and 739 ± 123 ms, P < 0.05; RMSSD: 12 ± 5 vs 23 ± 19 and 40 ± 32 ms, P < 0.05). Thus, HRV analysis in the baseline supine position was not a predictor of HUT outcome in patients with suspected NMS. Syncope during HUT seemed to be preceded by increased sympathetic activity manifested by an increase in heart rate and by a decreased parasympathetic tone manifested by a decrease in RMSSD measured for 5 minutes before the event, in comparison with HUT-negative patients and with controls.     

Postpartum Syncope

Recurrent unexpected syncope may have severe consequences and result in serious injury. This is especially the case in the immediate postpartum period when maternal syncope may have a disastrous effect on the infant as well as the mother. We report on 12 women who developed episodic hypotension resulting in syncope in the immediate postpartum period and describe the distinguishing characteristics of their presentation, tilt table results, and responses to therapy. Postpartum syncope represents a unique subgroup of syncopal patients who need to be recognized and treated in order to prevent potentially serious injury to both mother and infant.     

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.     

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.     

Recurrent Symptoms after Ventricular Pacing in Unexplained Syncope

We report clinical and hemodynamic data in two cases of recurrent syncope. Both patients received permanent demand ventricular pacing (VVI) for unexplained syncope. Both patients experienced recurrent syncope after pacemaker implantation. They later underwent 60 degrees head-up tilt testing, initially noninvasively and then with hemodynamic profile. A vasovagal response to tilt occurred with bradycardia and was complicated by the onset of ventricular pacing and retrograde atrioventricular conduction (RAVC) with hemodynamic deterioration and rapid reproduction of syncope. Limited intracardiac electrophysiological study (EPS) excluded atrioventricular (AV) conduction disease, sinus node disease, and carotid sinus syndrome, and confirmed RAVC. Both patients were upgraded to dual chamber pacing, DDI mode, with 50/80 rate hysteresis. One patient was asymptomatic at repeat tilt testing; the other experienced continued symptoms due to the vasodepressor component of vasovagal syncope. Cardiac pacing alone is ineffective treatment for this phenomenon, and no proven therapy is presently available. Ventricular pacing applied to patients with unexplained syncope may lead to an increase in or continuation of symptoms rather than an amelioration. There is a need for full investigation of such patients, which must include tilt testing, to allow for the most accurate diagnosis possible and guide the most appropriate therapy.     

Tolerance to Lower Body Negative Pressure Exposure: Comparison Between Patients with Neurocardiogenic Syncope and Controls

Lower body negative pressure exposure (LBNPE) produces hemodynamic modifications similar to those produced by head-up tilt test (HUT). Patients with vasovagal syncope are more susceptible to HUT than healthy persons. The supine position during LBNPE would facilitate the simultaneous performance of complementary methods. The aim of this study was to compare tolerance to LBNPE between a group of patients with vasovagal syncope and a group of healthy volunteers. Eleven patients with vasovagal syncope and positive HUT and 13 healthy volunteers without prior history of syncope and negative HUT were included. The following protocol was used: −10 mmHg, 1 minute; −20 mmHg, 1 minute; −30 mmHg, 3 minutes, and −40, −50, −60, and −70 mmHg, 5 minutes for each stage. Tolerance was expressed as: maximum tolerated negative pressure (Max NP), maximum tolerated time (Max T), and Σ P × T, where P = pressure and T = time. Syncope or presyncope during the test was considered positive LBNPE. LBNPE was positive at −50 or −60 mmHg in 8 of 11 patients (73%). One healthy volunteer had presyncope after 5 minutes at −70 mmHg. Tolerance, as expressed by any of the three parameters, was significantly higher for the healthy volunteers (Max NP: −59.1 ± 7.9 vs −70, P < 0.01; Max T: 19.1 ± 4.2 vs 24.4 ± 0.3, P < 0.01; Σ P × T: 836.3 ± 269.5 vs 1214.6 ± 18, P < 0.01). We conclude that patients with neurocardiogenic syncope have a significantly lower tolerance to LBNPE than subjects with no previous history of syncope.     

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.