Provocation of Bradycardia and Hypotension by Isoproterenol and Upright Posture in Patients with Unexplained Syncope

Abstract

Neurally mediated hypotension and bradycardia are believed to be common causes of syncope. We used the "upright-tilt test" (duration, less than or equal to 10 minutes) with or without an infusion of exogenous catecholamine (isoproterenol [1 to 5 micrograms per minute], given intravenously) to elicit bradycardia, hypotension, or both in 24 patients with recurrent syncope and in 18 control subjects. A conventional electrophysiologic test performed before the tilt test was positive in 9 of the 24 patients, revealing arrhythmias that may have caused recurrent syncope, but was negative and thus nondiagnostic in 15 patients. The tilt test alone (i.e., without isoproterenol) induced symptomatic bradycardia or hypotension in 1 of the 9 patients with positive electrophysiologic tests (11 percent), 4 of the 15 patients with negative electrophysiologic tests (27 percent), and none of the controls. When the isoproterenol infusion was administered during the tilt test, 9 of the 11 patients with negative electrophysiologic and tilt tests had syncope, marked slowing of the heart rate, and hypotension. In contrast, isoproterenol was associated with tachycardia and only a slight decline in arterial pressure in the 8 remaining patients with positive electrophysiologic tests and the 18 control subjects, and syncope developed in only 1 of the 8 patients with positive electrophysiologic tests and negative tilt tests (13 percent) and 2 of the 18 control subjects (11 percent). We conclude that an isoproterenol infusion administered in conjunction with the upright-tilt test may be useful for identifying susceptibility to neurally mediated recurrent syncope.

An Increased Endothelial‐Independent Vasodilation Is the Hallmark of the Neurally Mediated Syncope

“…The deep vasodilator response to the nitrate administration, reported to occur in skeletal muscle district during the vasovagal syncope, seems to be typical of the NMS and likely is a dose-independent phenomenon 20,21 ; this phenomenon indeed seems to suggest an abnormal vascular reactivity that could explain the poor efficacy of the pharmacologic therapy in this setting of patients. All the drugs tested, even using several targets to counteract the reflex response or to enhance the vasoconstriction, were usually reported to be poorly effective.…”

Non‐Pharmacological Management of Neurocardiogenic Syncope

“…4,6) However, in a recent double-blind, randomized, placebo-controlled study, atenolol was no more effective than placebo in tilt-positive syncopal patients. 20) Disopyramide, which inhibits the positive inotropic activity of the heart and the efferent parasympathetic outflow, was expected to prevent neurocardiogenic syncope.…”

“…1) It is typically triggered by environmental, physical or mental stress, with an estimated life-time prevalence of 35%, [1][2][3] and is diagnosed by head-up tilt testing. 4,5) A wide variety of treatments for recurrent neurocardiogenic syncope has been proposed, including beta-adrenergic blockade, [4][5][6] disopyramide, 7) and cardiac pacing, 8) though none is evidence-based. 9,10) Therefore, the choices have been mostly empiric, on the basis of mechanisms commonly believed to cause neurocardiogenic fainting.…”

Hemodynamic significance of heart rate in neurally mediated syncope

“…9,[18][19][20] Patients with otherwise unexplained syncope and a positive tilt test are assumed to suffer from vasovagal/vasodepressor syncope. We thus conducted this study to investigate the hemodynamic significance of HR in tilt-induced neurally mediated syncope.…”