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.     

Role of Vagal Control in Vasovagal Syncope

SUZUKI, M., et al .: Role of Vagal Control in Vasovagal Syncope. The vasovagal reaction is thought to be caused by sympathetic withdrawal and vagal augmentation. While measurements of muscle sympathetic nerve activity support sympathetic withdrawal in tilt induced syncope, the results of previous attempts to quantify vagal control using spectral analyses of heart rate variability (HRV) remain controversial. The sampling period used in the HRV studies is related to the discordant results. In the present study, HRV was computed every second using wavelet transformation to clarify the role of vagal control in tilt induced syncope during the 80-degree head-up tilt test (positive: 10 patients with vasovagal syncope; negative: 10 patients with vasovagal syncope, and 10 control subjects). Autonomic modulations were assessed using the absolute power of the low frequency (LF) (0.04–0.15 Hz) and high frequency (HF) (0.15–2.00 Hz) oscillatory components of R-R variability. Although the LF did not change during the tilt procedure, a decrease in the systolic arterial pressure (SAP) and increases in the R-R interval and HF were observed for the last 30 seconds before the tilt induced syncope in the tilt-positive group. Analyzing the hemodynamic measurements and spectral indices for the last 5 minutes preceding the tilt induced syncope, the study found that the SAP, R-R interval, and HF changed simultaneously during the 30-second period immediately before the tilt induced syncope. Further, the HF was positively correlated with the R-R interval and negatively correlated with the SAP. In conclusion, continuous spectral analysis of the R-R interval demonstrated increased vagal influence on the heart in tilt induced syncope. (PACE 2003; 26[Pt. I]:571–578)     

Detecting Incipient Vasovagal Syncope: Intraventricular Acceleration

The peak endocardial acceleration (PEA) caused by ventricular isometric contraction can be measured with an implantable microaccelerometer located inside the tip of a normal unipolar pacing lead. It has been shown that PEA correlates with myocardiai contractility and the maximum rate of rise of ventricular pressure (peak dP/dt) of the left ventricle. A PEA measuring system was temporarily inserted into the apex of the right ventricle in seven patients affected by syncope of uncertain origin. Each patient subsequently underwent 60 tilt testing with three different protocols: without pharmacological challenge (baseline); potentiated with sublingual trinitroglycerin (at a dose of 0.3 mg); and with isoproterenol infusion (at a dose of 3 μg/min). Each phase lasted 20 minutes. Syncope was induced in 1 patient during the baseline phase, in 3 patients during the trinitrin phase, and in 4 patients during the isoproterenol phase. Six patients had a negative response during the baseline phase and served as a control group. From the beginning of upright posture to the time of maximum heart rate, PEA increased by about the same amount in both positive and negative patients, but absolute values were from two- to three fold higher with isoproterenol (from 1.2 ± 0.5 G to 1.6 ± 0.8 G, from 0.8 ± 0.2 G to 1.2 ± 0.4 G, and from 2.8 ± 1.8 G to 3.6 ± 1.8 G, respectively, for negative, positive baseline or trinitrin, and positive isoproterenol tests). At the time of syncope, PEA values fell to baseline values. PEA changes were inversely correlated with blood pressure changes and directly correlated with heart rate changes. Thus, tilt induced syncope occurred both at low and high levels of left ventricular contractility. Whether spontaneous syncopes occur at low or high PEA behavior remains to be established. Since heart rate correlates well with changes in PEA and is far easier to measure, it is unlikely that a PEA measurement system or, in general, a contractility-based system, might become an ideal sensing parameter for the introduction of devices to combat vasovagal syncope.     

Evaluation of Sinus and Atrioventricular Nodes Function in Patients with Vasovagal Syncope

Aim: Evaluation of sinus and atrioventricular nodes function as a potential factor responsible for prolonged bradycardia, asystole, or both in patients with cardioinhibitory and non-cardioinhibitory vasovagal syncope (VVS). The study included 258 patients (mean age = 47.7 ± 17.2 years; range 18–62; 147 females) with a history of VVS. They were divided among four groups, according to results of head-up tilt test (HUTT).
Methods: All patients underwent standard HUTT, carotid sinus massage (CSM), and rapid transesophageal atrial pacing for evaluation of total sinus node recovery time (SNRT), and corrected sinus node recovery time (CNRT), resting and intrinsic heart rate (IHR), and Wenckebach point (WP). Values of SNRT > 1,500 ms, CNRT > 525 ms, WP < 130 bpm, and CSM-induced pause >3 seconds were considered abnormal.
Results: SNRT, CNRT, and WP before and after pharmacological blockade, resting heart rate, and IHR did not differ significantly among the study groups. The prevalence of mild sinus node dysfunction (SND), decreased value of WP, and cardioinhibitory carotid sinus hypersensitivity was similar among all study groups.
Conclusions: The prevalence of mild SND, abnormal atrioventricular conduction, and carotid sinus hypersensitivity (CSH) was similar among patients with VVS regardless of the type of vasovagal reaction. SND and CSH do not seem to play an important role in the pathogenesis of cardioinhibitory vasovagal reaction.     

Autonomic Imbalance Assessed by Heart Rate Variability Analysis in Vasovagal Syncope

In this prospective study, the autonomic modulation of the sinus node of 12 patients (mean age 28 ± 7 years) suffering from vasovagal syncope (VVS) was compared to that of 11 sex and age matched control patients (mean age 32 ± 4 years) by analysis of heart rate variability. Spectral indices (low frequency power [Plf], high frequency power [Phf], total power [Pt], sympathovagal balance [LF/HF]) and temporal indices, the mean of all coupling intervals between normal beats (mRR), the standard deviation about the mean (sdRR), the percentage of adjacent R to R intervals differing by more than 50 msec (pNN50), and the root mean square of variations in successive R to R intervals (rMSSD) were compared at baseline and during head-up tilt between and within groups. Baseline results were similar in both groups. During tilt testing, comparison of results between groups revealed only significantly higher sdRR and rMSSD and lower LF/HF ratio in VVS patients. Within WS patients, comparison of temporal and spectral analysis between baseline and tilt showed a significant increase of most indices (Plf, Phf, Pt, sdRR, and rMSSD) but a comparable LF/HF ratio; in contrast, control patients exhibited only a significant increase of LF/ HF ratio. In conclusion. VVS patients who developed vasovagal syncope during head-up tilt demonstrated a nonreciprocal modulation of the sinus node by the autonomic nervous system indicative of a pronounced physiological sympathetic surge along with a paradoxical vagal input to the cardiovascular system.     

Vasovagal Syncope: Diagnostic Role of Head-Up Tilt Test in Patients with Positive Ocular Compression Test

We investigated the relative merits of the ocular compression test and the head-up tilt test to aid differentiation of syncope and seizures in young patients. Sixteen patients (10 males and 6 females) with a mean age of 14 ± 4.7 (SD) years (range 7–22 years) underwent graded head-up till (15°, 30°, and 45° for 2 minutes each, then 60° for 20 minutes) following positive ocular compression testing defined as precipitation of asystole for at least 3 seconds (mean 5 seconds ± 2 seconds, range 3–12 seconds). Each patient presented with recurrent unexplained loss of consciousness (mean number of episodes 30 ± 45, mean duration of illness 52 ± 40 months), and seven patients were receiving anticonvulsant medications, three of these had normal EEGs. Eleven patients (69%) developed vasovagal syncope during head-up tilt, reproducing their clinical episodes (systolic blood pressure decreased from 105 ± 10 mmHg to 84 ± 13 mmHg, diastolic blood pressure from 75 ± 9 to 22 ± 25 mmHg, and heart rate from 89 ± 13 beats/mm to 37 ± 20 beats/min). Asystole occurred in two patients during vasovagal syncope lasting 11 seconds in one and 16 seconds in the other, and, it was associated with myoclonic movements in both (convulsive syncope). Based on these findings, and given the perceived potential hazards of the ocular compression test, the head-up tilt test may be a safer procedure that adds useful information to the diagnostic evaluation of these patients.     

Holter Monitoring vs Tilt Testing in the Investigation of Suspected Vasovagal Syncope

The aim of this study was to compare the diagnostic yield of 48-hour Holter monitoring with head-up tilt (HUT) test in patients presenting with blackouts suggestive of vasovagal syncope. One hundred and eighteen consecutive patients, 68 women, aged (mean [SD])   50 ± 20  years   (range 16–88 years), underwent 48-hour Holter monitoring and 60° HUT test within 3 months. Endpoints were symptom-ECG correlation during Holter monitoring and positive HUT test. Syncope occurred in 3 (3%) patients during Holter monitoring, the rhythm being sinus tachycardia in all. Presyncope was reported in 22 (19%), the rhythm being sinus tachycardia in 6, persistent atrial fibrillation in 2, and normal sinus rhythm in the remainder. Asymptomatic arrhythmias were recorded in 103 (87%) patients. Positive HUT tests occurred in 39 (33%), the pattern being mixed (VASIS type 1) in 14 (36%), cardioinhibitory (VASIS type 2) in 3 (8%), and vasodepressor (VASIS type 3) in 22 (56%). Change in patient management occurred in 3 (3%) patients following Holter monitoring and 39 (33%) patients following HUT test. Holter monitoring produces a low yield of clinically useful information in the investigation of suspected vasovagal syncope. An HUT test should be considered the primary investigation of choice in such patients. (PACE 2003; 26[Pt. I]:1523–1527)     

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.     

Vasovagal Syncope During Rectosigmoidoscopy: Report of a Case

Cardioinhibitory vasovagal syncope with sinus arrest and asystole of 28 seconds' duration occurred during rectosigmoidoscopy in a patient with frequent previous symptoms and a syncopal episode. A ventricular inhibited pacemaker was implanted and the patient has remained asymptomatic for 18 months.     

First Steps Toward a Pacing Algorithm for Vasovagal Syncope

Vasovagal syncope is commonly associated with an intermediate fall in heart rate. Consequently, it seemed possible that a pacemaker algorithm designed to detect intermediate heart rate falls might prove useful as a diagnostic tool to initiate pacing therapy. Subsequent experience suggests that with such an approach it is still difficult to avoid "false-positive" detection of physiologic heart rate slowing (e.g., sleep). On the other hand, findings from several reports suggest that high rate pacing using this algorithm has proved clinically effective.     

The Economics of Treating Vasovagal Syncope

The economics of treating vasovagal syncope depends on the severity of attacks. In patients with syncope without warning in whom injury is a consideration, a correctly chosen cardiac pacemaker may be warranted. Based on a recent appraisal of the cost effectiveness of dual versus single chamber pacing, it is possible to estimate the economic value of cardiac pacemakers for vasovagal syncope. Findings indicate that an economic argument favors pacing patients with severe vasovagal syncope. However, prospective study examining syncope recurrence rates in paced and nonpaced patients is not currently available.     

Autonomic Nervous System Changes in Vasovagal Syncope:

Spectral analysis of heart rate variability was used to compare the changes in autonomic function during tilting in young and older patients with vasovagal syncope. Twenty-four young (age 28 +/- 8 years) and 31 older (56 +/- 5 years) patients with unexplained syncope and a positive tilt test and 25 controls (age 48 +/- 12 years) were included in the study. Frequency-domain measurements of the low (LF) (0.06-0.15 Hz) and high (HF) (0.15-0.40 Hz) frequency bands and the ratio of LF to HF were computed from Holter recordings for 4-minute intervals before and immediately after tilting and just before the end in all groups. Syncopal patients showed a different pattern of response to tilting from controls in all spectral indexes. Young and older patients showed the same pattern of changes in all measurements, even though certain differences were observed. The LF after tilting reduced more in the older (-20 +/- 7% vs -14 +/- 5%, P < 0.001), while HF reduced more in young patients (-17 +/- 8% vs -8 +/- 3%, P < 0.001). Young patients showed mainly a cardioinhibitory type (71%) of response whereas a vasodepressor type response predominated (68%) in the older patients. The autonomic nervous system appears to play an important role in the pathophysiological mechanism of vasovagal syncope. This role is similar in young and in older patients and this should be taken into account in the therapeutic approach to the condition. Specific differences between age groups may be related to the type of vasovagal syncope.     

循环系统症状为主的血管迷走性晕厥误诊分析

目的　探讨非器质性疾病患者循环系统症状的原因。方法　对排除器质性心脏病的 47例患者进行倾斜试验。结果　在试验中 36例呈现阳性结果 ,占 76 .6 % ,均伴随其主诉症状的发生。结论　以循环系统症状为主而无客观证据的患者可能是一种特殊类型的血管迷走性晕厥。     

Usefulness of Plasma Catecholamines During Head-Up Tilt as a Measure of Sympathetic Activation in Vasovagal Patients

Vasovagal syncope is a common clinical disorder which has been traditionally related to a vasovagal reflex precipitated by an initial excess sympathetic stimulation. We hypothesized that the increase in plasma Catecholamines during head-up tilt is more accentuated in patients with tilt induced vasovagal syncope. To test this hypothesis, plasma Catecholamines were measured in supine posture and during head-up tilt in patients with a history suggestive of vasovagal syncope. Of these, 13 had a normal response to tilt (nonvasovagal group; age 41 ± 19 [SD]years) and 11 had a vasovagal response to tilt (vasovagal group; 39 ± 20 years). In the supine posture at rest, plasma epinephrine and norepinephrine were not significantly different between the nonvasovagal and the vasovagal groups (39 ± 28 ng/L vs 46 ± 38 ng/L, P = 0.5792, 335 ± 158 ng/L vs 304 ± 124 ng/L, P = 0.6007, respectively). Furthermore, the tilt induced changes in plasma epinephrine and norepinephrine were not different between the two groups (20 ± 20 ng/L vs 35 ± 55 ng/L, P = 0.3562, 264 ± 158 ng/L vs 242 ± 205 ng/L, P = 0.7724, respectively) suggesting that differences in the hemodynamic response to tilt are not predictable by the supine levels of circulating plasma Catecholamines, and that the extent of plasma catecholamines increase during tilt does not determine the hemodynamic outcome of the tilt test. Since orthostatic changes of plasma Catecholamines could be influenced by volume factors, we assessed plasma renin activity and aldosterone as surrogates of blood volume. Baseline plasma renin activity and aldosterone were not significantly different between the two groups. We conclude that inasmuch as plasma catecholamines reflect the status of sympathetic activity, our data do not support the hypothesis that accentuation of sympathetic activity precedes necessarily the tilt induced vasovagal syncope. However, one should take in consideration that multiple factors may influence catecholamine levels and catecholamines kinetics. A hyperresponsiveness of β-receptors to Catecholamines in patients with vasovagal syncope may be suggested but needs to be tested.     

Evaluation of a Single Stage Nitroglycerin Tilt Table Test for Diagnosis of Neurally Mediated Syncope

The purpose of this study was to compare clinical outcomes between a single stage head-up tilt table test (HUT) with infusion of 3.44 microg/kg per hour of nitroglycerin and a conventional multistage test with infusion of nitroglycerin from 1.72 microg/kg per hour to 5.16 microg/kg per hour in five successive stages. Thirty-seven patients with recurrent syncope underwent both tests in a prospective, randomized, crossoverfashion. During single stage HUT, a positive response occurred in 24 (64.9%) patients with unexplained syncope, an exaggerated response occurred in 3 (8.1%), a negative response in 7 (18.9%), and drug intolerance in 3 (8.1%). During the multistage HUT, these percentages were 62.2%, 16.2%, 13.5%, and 8.1%, respectively. Twenty healthy control subjects were involved in both tests, One of the control subjects had a positive response to single stage HUT, and two (10%) patients to multistage HUT. The duration of the test in single stage HUT was shorter than that in multistage HUT (8.6 +/- 10.3 vs 38.6 +/- 32.1 minutes, P < 0.01). The results showed that the single stage HUT was a fairly sensitive, specific, and a time-efficient test for provoking neurally mediated syncope.     

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.     

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.     

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)