Syncope in young persons frequently occurs in settings of emotional distress (for example, undergoing or witnessing a minor medical procedure). This type of syncope is called "vasodepressor" syncope because a decline in total peripheral vascular resistance causes decreased cerebral perfusion and loss of consciousness [1]. An additional factor contributing to the syncope is the occurrence of bradycardia in the face of systemic hypotension, a development that further compromises cerebral perfusion.

We describe the results of noninvasive tests of neurocardiovascular function in young persons who fainted while experiencing an event they perceived as emotionally distressing. The study was done to determine if fainters differed from nonfainters in those cardiovascular and cardiorespiratory reflexes that can be routinely assessed. Individual results were normal according to generally accepted criteria. Further analysis, however, showed that, as a group, those who experienced emotional event-related syncope differed from nonfainters in vagally mediated cardiac responses. The results offer insight into the pathophysiologic mechanisms underlying the most common form of syncope.

Methods

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In 1990-1991, 60 young persons, 15 to 17 years old, were evaluated because they had experienced one or more episodes of syncope during emotionally distressing events: These events included minor nonpainful medical procedures (31 patients), school examinations (12 patients), funerals (7 patients), hospital visits (4 patients), witnessing of traffic accidents (4 patients), conflicts with military recruiting authorities (1 patient), and conflicts with the police (1 patient). Forty-one patients were female. Eighty-four episodes of syncope were reported. Thirty-eight patients had a single episode of syncope, 20 had two episodes, and 2 had three episodes. Patients were studied from 7 to 34 days after the most recent episode of syncope (mean duration, 15 days). All patients who were referred for evaluation during the study period were included in the analysis.

All patients were referred by their family physicians and underwent a neurologic and cardiologic evaluation, which included a detailed history of each event; neurologic and cardiologic clinical examinations; and electroencephalographic, electrocardiographic, and echocardiographic studies. Additional clinical evaluations were done at the discretion of the examining neurologist and cardiologist and included electroencephalographic evaluation during sleep, computed tomographic scan of the brain, and Holter electrocardiographic monitoring. All test results were normal. Results of routine hematologic and blood chemistry laboratory studies were normal. No neurologic or cardiac causes of syncope were identified.

Controls included 40 healthy young persons, 15 to 17 years old, who had served as part of a large (n = 196), population-based control group in a previous study. They were all residents of northern Israel, the region that serves as the referral base for our institution. The group included 25 women.

Neurocardiovascular reflex testing was done in the morning hours. Patients fasted before testing but were encouraged to drink water freely. After emptying their bladders, patients were allowed 30 minutes of supine rest in a darkened room. An electrocardiogram was obtained with a Fukuda Denshi FCP2201 electrocardiograph (Fukuda Denshi Co., Ltd., Tokyo, Japan) that calculated the resting heart rate corresponding to the mean R-R interval at rest and the PR and QT_c (QT interval corrected for rate) intervals. The PR interval was calculated from the average of the intervals in the frontal plane leads. The QT_c was calculated from the average of all 12 leads.

The neurocardiovascular reflex tests included evaluation of the baroreceptor reflex arc and cardiorespiratory vagal function. The patients were instructed in controlled deep breathing at a respiratory rate of 6 breaths per minute. A musical metronome set at 1 beat/s was used to guide the patient in breathing with a respiratory cycle of 10 seconds. The minimal and maximal R-R intervals were determined from a recorded segment of 100 R-R intervals obtained during deep breathing. The minimal heart rate occurs during expiration as the result of increasing vagal parasympathetic tone. The maximal heart rate occurs during inspiration as the result of withdrawal of vagal tone. The difference, termed the inspiratory-expiratory difference, is a quantitative measure of the respiratory sinus arrhythmia and cardiac vagal parasympathetic innervation. The normal inspiratory-expiratory difference has been variously defined. One widely applied criterion is an inspiratory-expiratory difference of more than 15 beats/min at any age [2]. Weiling and colleagues [3] studied the effect of age on the inspiratory-expiratory difference (IEDiff) and reported a regression equation where log IEDiff = 1.5732-0.0060 (age). Given the age of our patients, the 95% CI for the inspiratory-expiratory difference was 16 to 50 beats/min [3].

The heart rate response to the Valsalva maneuver was measured from the electrocardiogram, which was acquired on-line using a personal computer connected to two surface chest electrodes oriented to approximate lead I. Using the R-wave recognition program, we calculated R-R intervals before, during, and after the period of "strain" and calculated the Valsalva ratio from the minimal R-R interval in phase II and the maximal R-R interval from phase IV of the maneuver [4]. The patient performed the Valsalva maneuver by blowing through a rubber tube attached to a mercury blood pressure manometer and maintained a pressure of 40 mm Hg for 15 seconds. A leak was introduced into the system by inserting a 22-gauge needle into the tubing. This requires the patient to keep the glottis open and maintain an intraoral pressure equal to the intrathoracic pressure during the entire maneuver. Patients were allowed a trial to appreciate the respiratory effort involved, the procedure being repeated after 5 minutes of rest. It has been shown that the results from a first well-performed effort do not differ from the averaged results of three efforts, and none of the young persons failed to perform the test as required the first time [5]. The Valsalva ratio is considered to be normal if 1.5 or higher, but a ratio of 1.25 or higher has also been suggested to avoid false-positive interpretations [4, 6]

Blood pressure was measured using a mercury manometer. Measurements were done with the patient supine and then after 1, 3, and 5 minutes of motionless standing.

The statistical significance of the difference in means was determined by the Student t-test for unpaired samples ( = 0.05). Correlation coefficients are Pearson coefficients.

Results

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Descriptive statistical results are summarized in Table 1. The inspiratory-expiratory difference and the Valsalva ratio in all patients were normal according to the criteria described above. Sinus bradycardia (resting heart rate of 52 to 59 beats/min) was noted in some patients. Although results fell within accepted normal limits, large, statistically significant differences were found between fainters and nonfainters.

View larger version (22K): [in this window] [in a new window]   Figure 1. Inspiratory-expiratory difference in heart rate in persons with syncope and in controls.

View larger version (19K): [in this window] [in a new window]   Figure 2. The Valsalva ratio in persons with syncope and in controls.

No statistically significant differences were found between fainters and nonfainters with respect to PR interval, QT_c interval, or change in systolic, diastolic, or mean blood pressure on motionless standing.

Discussion

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Fainting in the setting of acute emotional distress is the most frequently encountered type of syncope in young persons. Such fainting affects 15% to 25% of adolescents but is less common after 30 years of age [1]. This type of syncope is usually called vasodepressor syncope.

Recent reviews have focused on vasodepressor syncope, particularly its association with upright tilt testing with or without simultaneous isoproterenol infusion [7-11]. The primary event appears to be a decline in peripheral vascular resistance and hence in blood pressure. Cardiac output declines even further because of the development of an apparently paradoxical bradycardia in the face of hypotension [1].

Factors that remain unclear include the mechanism underlying the decline in peripheral resistance and the reason for the inappropriate bradycardia. Patients with vasodepressor syncope seem to be in a state of sympathetic activation as indicated by an increase in urinary catecholamine levels before syncope [11]. Sudden cessation in sympathetic activity to muscle before syncope has nevertheless been shown [12]. Whether resulting from cessation of sympathetic vascular innervation or from a posture-related shift of blood volume to the abdomen and legs [1], the final consequence is marked systemic hypotension. The anticipated cardiac response to this sequence of events would be an increased heart rate produced in part by a baroreceptor-mediated withdrawal of vagal tone. In patients prone to vasodepressor syncope, bradycardia occurs. A proposed mechanism of the bradycardia is activation of cardiac mechanoreceptors by vigorous myocardial contraction around a reduced ventricular volume, similar to the Bezold-Jarisch reflex [13-15]. In patients who experience vasodepressor syncope, the result is an inadequate increase in cardiac output and an accentuation of the hemodynamic factors favoring reduced brain perfusion with resulting loss of consciousness. One would speculate that the cardioinhibitory response might be more intense in patients with a high previous vagal parasympathetic tone.

The resting heart rate reflects the balance of parasympathetic and sympathetic influences at the sinoatrial node, with a lower rate indicating a greater parasympathetic vagal influence. In our study, the resting heart rate in the young persons with syncope was significantly slower than that in nonfainters, a reflection of a greater vagal tone at rest.

The inspiratory-expiratory difference in heart rate is an expression of vagally mediated heart rate variability that results only from the phasic changes in parasympathetic innervation of the sinoatrial node during breathing. The significantly greater inspiratory-expiratory difference among the persons with syncope indicates a more powerful vagal influence and a higher vagal tone than in the nonfainters.

The heart rate changes during the Valsalva maneuver are mediated by autonomic reflexes in response to changes in blood pressure. The reduced cardiac output and hypotension during the phase II period of "strain" produces a reflex-mediated cardioacceleration and peripheral vasoconstriction. When venous return is increased after the release of "strain," the suddenly greatly increased cardiac output encounters a constricted vascular bed, producing an increase in blood pressure over the resting level. This hypertension is associated with a vagally mediated cardiac deceleration in phase IV of the maneuver [4]. The Valsalva ratio, the ratio of the heart rates in phases II and IV, has long been used to identify reduced vagal function in patients with diabetic autonomic neuropathy [6]. We suggest that the higher Valsalva ratio in persons with syncope indicates that they had a greater vagal tone compared with nonfainters. Support for this suggestion is seen in the significant negative correlation between the Valsalva ratio and the resting heart rate.

As we have noted, fainting in an emotionally unpleasant situation, although common in very young persons, becomes less common with increasing age. Cardiac vagal tone is well known to decrease with increasing age, and both the inspiratory-expiratory difference and the Valsalva ratio show a linear reduction with increasing age [3, 16, 17]. We suggest that many young persons who experience emotional event-related syncope have a high vagal tone that predisposes to the cardioinhibitory component of the syncope, a mechanism that may be similar to the Bezold-Jarisch reflex. We further suggest that normal age-related reduction in cardiac vagal tone accounts, at least in part, for the reduction in the incidence of this type of syncope in adults.