title: Spontaneous vs nitroglycerin-induced vasovagal reflex on head-up tilt: Are there neuroendocrine differences?
abstract: 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.
authors.affiliation: Department of Clinical Sciences, Lund University, Clinical Physiology and Nuclear Medicine Unit, Skåne University Hospital, Malmö, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Nilsson
authors.affiliation: National Heart and Lung Institute, Imperial College, St. Mary's Hospital Campus, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
authors.affiliation: Department of Clinical Sciences, Lund University, Hypertension and Cardiovascular Disease Group, Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Department of Clinical Sciences, Lund University, Hypertension and Cardiovascular Disease Group, Clinical Research Centre, Skåne University Hospital, Malmö, Sweden,; Department of Cardiology, Skåne University Hospital, Malmö, Sweden. Electronic address: Artur.fedorowski@med.lu.se.
authors.forename: Artur
authors.initials: A
authors.lastname: Fedorowski
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000503:physiopathology*; D005996:Nitroglycerin / Q000008:administration & dosage*; D012018:Reflex / Q000187:drug effects*; D019462:Syncope, Vasovagal / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D018667:Tilt-Table Test; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D005996:Nitroglycerin
keywords: Catecholamine; Head-up tilt test; Neurohormone; Vasovagal syncope; vasopressin