Neurally mediated syncopal syndromes: pathophysiological concepts and clinical evaluation

The neurally mediated syncopal syndromes encompass a number of apparently related disturbances of reflex cardiovascular control characterized by transient inappropriate bradycardia and/or vasodilation of various arterial and venous beds. Certain of these syndromes (e.g., carotid sinus syndrome, postmicturition syncope) are encountered occasionally in clinical practice, whereas others are quite rare (e.g., swallow syncope). On the other hand, vasovagal syncope occurs so frequently, that as a group, the neurally mediated syncopal syndromes are among the most important causes of syncope. The pathophysiology of the neurally mediated syncopal syndromes is incompletely understood, but can be considered in terms of four basic elements: (1) the afferent limb; (2) central nervous system (CNS) processing; (3) the efferent limb; (4) feedback loops. The afferent limb consists of several peripheral and CNS trigger sites and the associated connections to medullary cardiovascular centers. CNS processing and efferent signals result in both bradycardia, which may be marked or relative, and vasodilatation. Failure of baroreceptor feedback controls to prevent hypotension is important in facilitating development of symptomatic hypotension. Head-up tilt table testing has become the diagnostic technique of choice for clinically assessing susceptibility to neurally mediated syncope, particularly of the vasovagal type. Most studies suggest that such testing discriminates relatively well between symptomatic patients and asymptomatic control subjects, of whom 10%-15% have a false-positive test results. Sensitivity of tilt table testing is more difficult to evaluate because there is no accepted diagnostic gold standard. However, sensitivity (measured against a classic presentation) has been estimated to range from 32%-85%, with most reports favoring the higher end of this range. Treatment strategies for neurally mediated syncope remain controversial. Many single episodes do not warrant treatment unless physical injury has occurred, or a high risk occupation or avocation is involved. Tilt test exposure alone may prove beneficial in educating patients with recurrent syncope to recognize warning signs of an imminent faint. Large controlled clinical studies have not been performed to test the efficacy of pharmacological therapy (e.g., beta-adrenergic blockers, disopyramide, serotonin reuptake blockers, vasoconstrictors) or pacing therapy. Such studies may be difficult to undertake due to the variable frequency of spontaneous symptoms and apparent long periods of remission. Nonetheless, many investigators and clinicians have come to rely on these agents, and on tilt testing to guide treatment decisions. Studies employing careful correlation of long-term clinical follow-up with results of early and perhaps later repeat tilt studies are still needed.