Age-dependence of relative change in circulating epinephrine and norepinephrine concentrations during tilt-induced vasovagal syncope

Background: Although vasovagal syncope (VVS) is preceded by a surge of circulating catecholamines (epinephrine [Epi] and norepinephrine [NE]) of adrenal/renal and synaptic origin, prevention of VVS with β-adrenergic blockade has been ineffective except in "older" VVS patients. Objective: We hypothesized that age-related differences of β-blocker effect may be due in part to differences in the relative magnitudes of Epi and NE release during an evolving faint, specifically, greater Epi/NE ratio in younger fainters compared to older patients. To assess this hypothesis, we measured changes in Epi/NE ratios in younger (<40 years) vs older (<40 years) patients during head-up tilt-table test-induced VVS. Methods: The study comprised 29 patients (12 patients <40 years [mean 56 ± 10.7 years] and 17 patients <40 years mean 25 ± 5.7 years]) with recurrent suspected VVS in whom 70° head-up tilt testing reproduced symptoms. Arterial Epi and NE concentrations were measured at baseline (supine), 2 minutes of head-up tilt, and syncope. Results: Baseline Epi and NE concentrations and the Epi/NE ratio did not differ in younger and older groups (Epi: 90 ± 65 pg/mL vs 70 ± 32 pg/mL; NE: 226 ± 122 pg/mL vs 244 ± 183 pg/mL). However, Epi/NE ratio increased to a greater extent in younger fainters during head-up tilt and tended to be greater in younger patients at both 2 minutes (<40: 1.02 ± 1.29 vs <40: 0.40 ± 0.27, P =.11) and at symptoms (<40: 2.6 ± 1.26 vs <40: 1.6 ± 0.71, P =.03). At symptoms, Epi/NE ratio <2.5 was observed in 9 of 17 younger patients vs 1 of 12 older patients (P =.02). Conclusion: Epi/NE ratios tend to be greater in younger fainters, a finding that may account in part for the observation that β-blocker therapy is less effective in reducing VVS susceptibility in younger individuals.