Orthostatic Versus Electrophysiologic Testing in Unexplained Syncope in Children and Adolescents

Orthostatic vs EP Testing in Pediatric Unexplained Syncope. Introduction: Unexplained syncope in the pediatric age group is a common problem that often requires cardiac evaluation. This work-up is expensive and frequently unrevealing. Electrophysiologic and, more recently, tilt table or orthostatic testing have been used in the evaluation of unexplained syncope. Methods and Results: We undertook to compare the results of these two forms of evaluation in a group of 26 young patients less than 19 years of age with episodes of unexplained syncope. Sixteen of the 26 patients (62%) had an abnormal electrophysiologic study with the majority having either mild sinus node dysfunction or inducible atrial flutter. Four of the 26 patients (16%) were thought to have an abnormality found that was clinically significant (sustained ventricular tachycardia [2], nonsustained ventricular tachycardia/polymorphic premature ventricular contractions [1], and high-degree atrioventricular block [1]). An abnormal response to orthostatic testing was found in 14 of 26 patients (56%) with 13 of 14 developing syncope at an average standing time of 6.5 minutes. Sixteen patients underwent treatment based on the study findings and follow-up with an average time of 1.6 years is available on 13 of 16 patients who underwent treatment. Of the nine patients treated for neurally mediated syncope (fludrocortisone [7], beta blocker [1], theophylline [1]), all are asymptomatic. The four patients with an arrhythmic cause of syncope found by electrophysiologic testing are asymptomatic on treatment (antiarrhythmic drug [3], permanent pacing [1]). Conclusion: Orthostatic testing has a higher positive yield than electrophysiologic testing in the evaluation of unexplained syncope in young patients. Orthostatic or tilt table testing should be considered early on in the cardiovascular evaluations of these patients. (J Cardiovasc Electrophysiol, Vol. 3, pp. 418–422, October 1992)     

Clinical spectrum of neurally mediated reflex syncopes.

AIMS: The clinical features of the various types of neurally mediated reflex syncope have not been systematically investigated and compared. We sought to assess and compare the clinical spectrum of neurally mediated reflex syncopes. METHODS AND RESULTS: Four hundred sixty-one patients with syncope were prospectively evaluated and 280 had neurally mediated reflex syncope. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. Typical vasovagal syncope was diagnosed in 39 patients, situational syncope in 34, carotid sinus syncope in 34, tilt-induced syncope in 142 and complex neurally mediated syncope (positive response to both carotid sinus massage and tilt test) in 31. The clinical features of situational, carotid sinus, tilt-induced and complex neurally mediated syncope were very similar. By contrast, typical vasovagal syncope differed from other neurally mediated syncopes not only in terms of its precipitating factors (fear, strong emotion, etc.), which constituted predefined diagnostic criteria, but also in the variety of its clinical features (lower age and prevalence of organic heart disease, higher prevalence of prodromal symptoms, and of autonomic prodromes, longer duration of prodromes, higher prevalence of symptoms during the recovery phase and lower prevalence of trauma). CONCLUSION: The clinical spectrum of neurally mediated reflex syncopes demonstrates much overlap between them. However, when the afferent neural signals are localized in cortical sites, as in typical vasovagal syncope, symptoms are more frequent and of longer duration.     

Management of Vasovagal Syncope

Vasovagal syncope is a common disorder of autonomic cardiovascular regulation that can be very disabling and result in a significant level of psychosocial and physical limitations. The optimal approach to treatment of patients with vasovagal syncope remains uncertain. Although many different types of treatment have been proposed and appear effective based largely on small nonrandomized studies and clinical series, there is a remarkable absence of data from large prospective clinical trials. However, based on currently available data, the pharmacologic agents most likely to be effective in the treatment of patients with vasovagal syncope include beta blockers, fludrocortisone, and alpha-adrenergic agonists. In this article, we provide a summary of the various therapeutic options that have been proposed for vasovagal syncope and review the clinical studies that form the basis of present therapy for this relatively common entity.     

Pathophysiology of reflex syncope: A review

In this correspondence, the pathophysiology of reflex syncope (vasovagal syncope, carotid sinus syndrome, and situational syncope) is reviewed, including clarification of the nomenclature.     

Troponin release after exertional vasovagal syncope

Troponin release following exertional vasovagal syncope has not previously been reported. A young man was investigated after being admitted twice with exertional syncope, each time followed by a 10‐fold spike in troponin I over 24 h. Treadmill exercise tests reproduced his symptoms and demonstrated a vasovagal mechanism. During recovery, despite lying supine, he remained hypotensive for 5 min, with profound bradycardia and ST segment depression. We suspected that intense cardiovagal neural activity may have caused the troponin leak.     

倾斜试验对原因不明晕厥的诊断价值

本文对１８例原因不明的晕厥患者和１５例无晕厥病史的正常人进行了研究。８例患者（４４％）在倾斜试验１８±７ｍｉｎ时出现阳性，对照组无一例阳性（Ｐ＜０．０１）。试验阳性患者收缩压从１４．４±２ｋＰａ（１０８±１５ｍｍＨｇ）降至８±２．２７（６０±１７ｍｍＨｓ）ｋＰａ（Ｐ＜０．０１），心率从７８±２３次／分增至８７±１７次／分（Ｐ＞０．０５）。倾斜试验期间，无任何临床症状可预测晕厥的发生。对照组试验前后心率及血压无明显差异（Ｐ＞０．０５）。倾斜试验对鉴别血管迷走性晕厥具有较好的诊断价值。该试验安全、无创、方便实用，是较理想的新的诊断方法。     

Familial vasovagal syncope.

Vasovagal syncope (VVS) is a common clinical problem characterized by transient episodes of loss of consciousness due to abnormal autonomic activity. This paper describes two groups of monozygotic twins, from different families, affected by VVS and a family with several members with this condition. Their clinical characteristics, haemodynamic response to tilt, treatment, and outcome are described.     

The diagnostic value of ATP testing in patients with unexplained syncope.

A minority of patients with unexplained syncope has an increased susceptibility to adenosine triphosphate (ATP) injection. In these 'hypersensitive' patients, owing to its powerful cardiac and hypotensive effects, endogenous adenosine released under physiological and pathological conditions could trigger bradycardia and/or hypotension and cause syncope. This hypothesis still needs to be proven. However, there is some evidence that the ATP test identifies a group of patients with otherwise unexplained syncope with definite clinical features, absence of structural heart disease and benign prognosis. The mechanism of syncope is heterogeneous; indeed, in cases of electrocardiographic documentation of spontaneous syncope, either a long ventricular pause (mainly due to paroxysmal atrioventricular (AV) block) or no rhythm variations or even tachycardia were documented. ATP-positive patients have clinical features and mechanisms of syncope which are different from tilt-positive patients. Owing to its low positive predictive value, the ATP test is of little value in selecting treatment. A favourable outcome suggests a strategy of postponing treatment, in particular pacemaker therapy, until a definite diagnosis can be made by documenting a spontaneous syncopal relapse.     

Haemodynamic changes early in prodromal symptoms of vasovagal syncope.

AIMS: Vasovagal syncope (VVS) is often preceded by prodromal symptoms. The haemodynamic changes occurring during the prodrome have not been systematically investigated. The aim of the present study was to investigate the behaviour of blood pressure (BP), heart rate (HR) and sympathetic activity at the beginning of the prodrome in patients with tilt-induced VVS. METHODS AND RESULTS: Sixty-three patients with VVS underwent tilt testing. BP and HR were measured and blood samples for plasma catecholamine determination were obtained during the test. Twenty-seven patients developed syncope of whom all had a prodrome. From the last scheduled measurement before prodromal symptoms to the beginning of the prodrome, both systolic and diastolic BP decreased in all patients (from 105 +/- 16 to 74 +/- 20 mmHg, P<0.001, and from 68 +/- 13 to 51 +/- 12 mmHg, P<0 001, respectively) and HR decreased in 18 (67%) (from 89 +/- 22 to 80 +/- 25 beats/ min P<0 02). At the onset of loss of consciousness both BP and HR showed a further decrease (P<0.001). Plasma adrenaline significantly increased from the last sample before prodromal symptoms to the beginning of the prodrome (P<0.01) and showed a further increase during loss of consciousness (P<0.05), whereas plasma noradrenaline did not increase, as an expression of inhibition of sympathetic neural outflow. CONCLUSION: These results demonstrate that in patients with tilt-induced VVS, BP is consistently decreased at the beginning of prodromal symptoms because of the withdrawal of sympathetic activity, and HR is often reduced, probably because of increased vagal activity. We may infer that similar haemodynamic features also occur during spontaneous VVS.     

Tilt table evaluation for control pediatric patients: Comparison with symptomatic patients

This study was designed to evaluate pediatric control patients during head-up tilt in comparison with symptomatic neurocardiogenic syncope patient head-up tilt responses. Twenty-three pediatric control (c) patients (13 females, 10 males; 11.9 ± 3.1 years) were tested with head-up tilt (HUT) and compared with 66 symptomatic (s) patients. Baseline drug-free HUT (cHUT-1), a second drug-free HUT (cHUT-2), and a final HUT with isoproterenol infusion (cHUT-3) were each performed at 80° tilt angle for 30 min or until positive. For comparison, 66 symptomatic patients (41 females, 25 males; 13.6 ± 2.5 years) underwent drug-free HUT (sHUT-1); negative responders during sHUT-1 underwent follow-up HUT with isoproterenol (sHUT-2). HUT data were compared for both groups at both 30 and 20 min tilt duration. Twelve control patients (52%) had a symptomatic response during cHUT-1 at 18±8 min. During cHUT-2, 5 of 23 patients were positive at 13±5 min; each had previously tested positive during cHUT-1. Two patients, each positive in cHUT-1 and cHUT-2, refused cHUT-3. The only patient testing positive during cHUT-3 was test positive in cHUT-1 but negative for cHUT-2. In comparison, 43 of 66 (65%) symptomatic patients tested positive during drug-free sHUT-1 at 11±6 min. Subsequently, 20 of the 23 negative patients underwent HUT with isoproterenol (sHUT-2), with 8 of 20 testing positive. Thus, 51 of 66 symptomatic patients (77%) were called “true positives.” Chi-square analysis for comparison of 30 min cHUT-1 (12/23 positive patients) versus sHUT-1 (43/66 positive patients) yielded no statistical difference. However, analysis of data limited to 20 min tilt duration showed 7 of 23 positive cHUT-1 versus 38 of 66 positive sHUT-1 patient responses (p = 0.025). It is concluded that (1) pediatric HUT is relatively nonspecific in a control population (52% false positive), (2) concordance for consecutive positive control tilts is low, (3) isoproterenol does not increase overall predisposition to positive pediatric control patient response, and (4) an 80° tilt protocol limited to 20 min duration may help differentiate between false and true positive responses.     

A case of nocturnal fainting: supine vasovagal syncope.

Supine loss of consciousness is a relatively rare occurrence prompting investigations for underlying causes as diverse as cardiac arrhythmia, hypoglycaemia and nocturnal epilepsy. Neurally mediated syncope is rarely implicated as the cause of symptoms in supine loss of consciousness because of the absence of orthostatic stress and gravitational relative preservation of cerebral perfusion, but we report here on a case of recurrent, atypical and troublesome vasovagal syncope occurring at night while supine. Diagnosis aided by head-up tilt table testing and conservative management brought about complete resolution of symptoms.     

Atrioventricular Dissociation Exacerbating Posturally-Induced Syncope

We report a case of an 85-year-old patient with posturally-induced syncope in whom symptoms were reproduced during tilt table testing in conjunction with development of an accelerated junctional rhythm with isorhythmic atrio-ventricular (AV) dissociation. That loss of AV synchrony was crucial to development of hypotension and syncope was demonstrated during electrophysiologic testing in which both an accelerated junctional rhythm and an inducible atypical AV nodal re-entrant tachycardia (AVNRT) were induced. The accelerated junctional rhythm was accompanied by moderate hypotension with the patient in the supine posture, whereas blood pressure was well maintained during atypical AVNRT despite a much faster ventricular rate. Thus, symptomatic hypotension due to AV dissociation, presumably the result of transient autonomic disturbance, may be another manifestation of neurally-mediated syncope.     

Prospective randomized study comparing permanent pacing with rate drop response and closed loop stimulation in patients with vasovagal syncope where permanent pacing is indicated and selected as the appropriate treatment option

Background

Pacing for vasovagal syncope is established. Two pacing algorithms are available. The rate-drop-response (RDR-Medtronic) is triggered by falling heart rate acting with modified rate-hysteresis. The closed loop stimulation or system (CLS-Biotronik) is triggered by impedance changes in the right ventricle reflecting falling volume and rising contractility. These are very different physiologically. Both algorithms carry favorable reports in clinical use.

Methods

A randomized-controlled superiority trial is proposed to compare the two algorithms for the control of vasovagal syncope in patients for whom pacing is indicated by current guidelines in North America and Europe. Available recent evidence may be seen as supporting superiority of CLS. No comparison between the two algorithms has been made. In this trial, patients will be centrally randomized to one or other algorithm on a 1:1 basis. Two-hundred-seventy-six patients in each group will be recruited. Sample size is determined using a confidence interval of 95%, a power of 90%, and a drop-out rate of 10% to detect an 11% difference between CLS and RDR. Recurrent symptom comparison will be made by an independent committee. The Co-primary endpoints will be recurrent syncope burden compared with that in 24-months preimplant, and occurrence of syncope in 24-months follow-up. Each outcome will be compared between the two algorithms. Secondary endpoints will be program and drug therapy changes over 24-months follow-up and quality of life by questionnaire at baseline,1 and 2 years.

Results and Conclusions

These are anticipated to clarify the device algorithm choice and, therefore, to improve patient care.