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

Abstract

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.

Keywords: catecholamines; epinephrine; head-up tilt test; syncope; vasovagal syncope.

Figure 1 -

Linear correlation model of relation between plasma epinephrine level at 2 minutes HUT (abscissa) and time to syncope (ordinate). Dashed lines indicate 95% confidence limits. y; regression line, R; correlation coefficient, R-squared; decision coefficient, P; P value.

Figure 2 -

Exponential correlation model of relation between epinephrine at 2 minutes of HUT (abscissa) and time to syncope (ordinate). R-squared; decision coefficient, P; P value.

Figure 3 -

Exponential correlation model examining the relation between the change of plasma epinephrine level from Baseline to 2 minutes HUT (abscissa) and time to syncope (ordinate). Data in men are shown in blue and women in orange. Logarithmic regression of this relation is provided in Figure 4.

Figure 4 -

Regression examining the relation between the time to syncope (ordinate) and that of the natural logarithm of the change of plasma epinephrine from baseline to 2 min of HUT. The correlation is statistically significant (P=0.0006). See Table 2 for the decision coefficients and P values for male and female separately. y; regression line, R; correlation coefficient, R-squared; decision coefficient, P; P value.