Spontaneous vs nitroglycerin-induced vasovagal reflex on head-up tilt: Are there neuroendocrine differences?

Background Head-up tilt test (HUT) has been used for nearly 30 years for diagnosing vasovagal syncope (VVS) and was enhanced by sublingual nitroglycerin (glyceryl trinitrate [GTN]) challenge in the 1990s. Objective The purpose of this study was to explore neuroendocrine differences between spontaneous and drug-induced HUT positivity. Methods Two hundred eighty-eight patients (41.3% male, age 49 ± 21 years) with either positive passive (n = 60 [20.8%], age 38 ± 17 years) or GTN-enhanced HUT (n = 228, age 51 ± 21 years) were assessed. Beat-to-beat hemodynamic data, plasma epinephrine, plasma norepinephrine, plasma renin, C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1, and mid-regional fragment of pro–atrial natriuretic peptide were measured resting supine and after 3 minutes of HUT. In multivariate–adjusted regression analyses controlling for age and gender, clinical, neuroendocrine, and hemodynamic parameters were compared between spontaneous and GTN-mediated positive tests. Results Patients with spontaneous VVS reported more syncope compared to those with GTN-mediated VVS (median interquartile range 6 [17] vs 4 [6], P = .002). There was no difference in resting concentrations of neurohormones between the 2 groups. However, after 3 minutes of HUT, those who later developed spontaneous VVS demonstrated higher levels of CT-proAVP (59.5 ± 137 vs 6.9 ± 4.6, P <0.001) and epinephrine (0.57 ± 1.43 vs 0.23 ± 0.19, P = .003), and lower blood pressure (119/73 vs 139/81 mm Hg, P <.001). Asystole during VVS was more common in the spontaneous VVS group (35% vs 17.5%, P = .016). Conclusion Patients with spontaneous VVS on HUT reported more syncopal events than those with drug-potentiated positive HUT, but both groups shared similar supine neuroendocrine profiles. However, spontaneous VVS during HUT is characterized by lower blood pressure, pronounced increases in epinephrine and vasopressin during early HUT phase, and higher frequency of reflex asystole. Head-up tilt test (HUT) has been used for nearly 30 years for diagnosing vasovagal syncope (VVS) and was enhanced by sublingual nitroglycerin (glyceryl trinitrate [GTN]) challenge in the 1990s. The purpose of this study was to explore neuroendocrine differences between spontaneous and drug-induced HUT positivity. Two hundred eighty-eight patients (41.3% male, age 49 ± 21 years) with either positive passive (n = 60 [20.8%], age 38 ± 17 years) or GTN-enhanced HUT (n = 228, age 51 ± 21 years) were assessed. Beat-to-beat hemodynamic data, plasma epinephrine, plasma norepinephrine, plasma renin, C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1, and mid-regional fragment of pro–atrial natriuretic peptide were measured resting supine and after 3 minutes of HUT. In multivariate–adjusted regression analyses controlling for age and gender, clinical, neuroendocrine, and hemodynamic parameters were compared between spontaneous and GTN-mediated positive tests. Patients with spontaneous VVS reported more syncope compared to those with GTN-mediated VVS (median interquartile range 6 [17] vs 4 [6], P = .002). There was no difference in resting concentrations of neurohormones between the 2 groups. However, after 3 minutes of HUT, those who later developed spontaneous VVS demonstrated higher levels of CT-proAVP (59.5 ± 137 vs 6.9 ± 4.6, P <0.001) and epinephrine (0.57 ± 1.43 vs 0.23 ± 0.19, P = .003), and lower blood pressure (119/73 vs 139/81 mm Hg, P <.001). Asystole during VVS was more common in the spontaneous VVS group (35% vs 17.5%, P = .016). Patients with spontaneous VVS on HUT reported more syncopal events than those with drug-potentiated positive HUT, but both groups shared similar supine neuroendocrine profiles. However, spontaneous VVS during HUT is characterized by lower blood pressure, pronounced increases in epinephrine and vasopressin during early HUT phase, and higher frequency of reflex asystole.