Impact of Cardiovascular Neurohormones on Onset of Vasovagal Syncope Induced by Head-up Tilt

Background Vasovagal reflex is the most common form of syncope, but the pathophysiological mechanisms that initiate the reflex are not well understood. We aimed to study supine and early orthostatic levels of the neurohormones involved in control of circulatory homeostasis in relation to the onset of tilt-induced vasovagal syncope (VVS). Methods and Results A total of 827 patients who were investigated for unexplained syncope with head-up tilt test (HUT) and optional nitroglycerin provocation (Italian protocol) had blood samples collected while supine and after 3-minutes of HUT. Of these, 173 (20.9%) patients developed VVS during drug-free HUT, 161 of whom (males 44.7%; age 45±21 years) had complete data. We analyzed levels of epinephrine, norepinephrine, C-terminal pro-arginine vasopressin, C-terminal endothelin-1, and midregional fragments of pro-atrial natriuretic peptide and pro-adrenomedullin in relation to time from tilt-up to onset of VVS. We applied a linear regression model adjusted for age and sex. The mean time to syncope was 11±7 minutes. Older age (β=0.13; SE=0.03, P