Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters

Ritsuko Kohno, Barry L.S. Detloff, Lin Yee Chen, Faye L. Norby, David G. Benditt

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22 Scopus citations


Background: Head-up tilt (HUT) is widely used for diagnostic evaluation of patients with suspected vasovagal syncope (VVS), but also offers an opportunity to study VVS pathophysiology. In this regard, it is known that plasma epinephrine (Epi) levels and Epi/norepinephrine (NE) ratio are markedly increased from baseline at the time of HUT-induced VVS. However, whether these changes contribute to VVS susceptibility remains uncertain. Objective: We hypothesized that if catecholamines contributed to VVS directly, then a greater increase of plasma Epi and Epi/NE ratio early during HUT would be associated with shorter time to syncope. Methods: The patient population comprised 33 individuals (14 men, 43 ± 2 years) with suspected VVS in whom 70° HUT reproduced symptoms. Arterial Epi and NE concentrations were collected at baseline (supine) and 2 minutes of HUT. Linear, exponential, and multiple regression were used to access the association between changing catecholamine levels and time to syncope. Results: Mean ± SD time to positive HUT was 11 (7.6) minutes. Higher plasma Epi levels (pg/mL) both at baseline and at 2 minutes upright correlated with shorter time to syncope (baseline, R = −0.35, P = 0.048; and 2 minutes, R = −0.58, P = 0.001). Similarly, a greater Epi/NE ratio at 2 minutes head-up correlated with earlier time to syncope (R = −0.49, P = 0.007). These relationships remained significant after adjusting for age and sex (P = 0.006 and 0.02, respectively). Conclusion: Greater Epi levels and Epi/NE ratio early during HUT were associated with shorter time to VVS, suggesting a possible contribution to VVS susceptibility.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalJournal of cardiovascular electrophysiology
Issue number3
StatePublished - Mar 2019

Bibliographical note

Funding Information:
David G. Benditt, MD, Cardiac Arrhythmia Center, Cardiovascular Division, University of Minnesota, Mail Code 508, 420 Delaware Street SE, MMC 508, Minneapolis, MN 55455. Email: [email protected] Dr Benditt was supported in part by a grant from the Dr Earl E. Bakken Family in support of Heart‐Brain research. Dr Chen was supported by research grants from the National Heart, Lung, and Blood Institute (R01HL126637 and R01HL141288)

Funding Information:
The authors thank many staff members of the Cardiac Electrophysiology Laboratory who assisted with these studies and the patients who consented to participate.


  • catecholamines
  • epinephrine
  • head-up tilt test
  • syncope
  • vasovagal syncope


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