title: Esmolol tilt testing with esmolol withdrawal for the evaluation of syncope in the young.
abstract: BACKGROUND
  Head-upright tilt (HUT) testing is valuable in evaluating syncope. Isoproterenol is used to increase sensitivity. However, isoproterenol is contraindicated or dangerous in undiagnosed heart disease and produces false-positives. We introduced esmolol withdrawal during esmolol HUT, hypothesizing that (1) acute withdrawal of the ultrashort-acting beta-blocker induces beta-adrenergic effects by unmasking endogenous catecholamines and may provoke syncope with fewer risks, and (2) response to esmolol/esmolol withdrawal may predict effective therapy.
  
  
  RESULTS
  Thirty-six patients with unexplained recurrent syncope/presyncope (7 to 35 years old, known heart disease or arrhythmia in 14) underwent 2 to 4 HUT tests (60 degrees, 49 minutes): (1) baseline, (2) esmolol (500 micrograms/kg plus 50 micrograms.kg-1.min-1), (3) esmolol withdrawal (HUT continued after esmolol stopped), and (4) isoproterenol if tests 1 through 3 were negative and isoproterenol was not contraindicated. A positive test reproduced symptoms with hypotension or bradycardia, requiring recumbency for recovery. Twenty-five had positive tests, and 11 had negative tests. In 5, only the baseline test was positive; in 15, esmolol/esmolol withdrawal tests were also positive, with 3 in whom esmolol withdrawal was positive although negative at baseline. Two isoproterenol tilts were positive. Esmolol withdrawal and isoproterenol tilts had the highest initial heart rate and similar maximal heart rate increment. Only isoproterenol caused hypertension. One isoproterenol test was false-positive, with hypertension-induced arterial baroreflex. Treatment was beta-blockers (8), Na/fludrocortisone (9), both (6), and DDD pacemakers (2). Esmolol/esmolol withdrawal accurately predicted therapeutic response in 15; isoproterenol predicted therapeutic response in none.
  
  
  CONCLUSIONS
  Esmolol withdrawal tilt testing is preferable to isoproterenol for provocative testing of syncope in the young, and it appears to be safer. Esmolol withdrawal testing has clinical utility before invasive testing as a first-line investigation for syncope in patients with or without heart disease.
authors.affiliation: Division of Pediatric Cardiology, University of Arizona Health Sciences Center, Tucson 85724.
authors.forename: M
authors.initials: M
authors.lastname: Ovadia
authors.forename: D
authors.initials: D
authors.lastname: Thoele
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D001919:Bradycardia / Q000175:diagnosis; D000075202:Contraindications; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000175:diagnosis; D007545:Isoproterenol; D008297:Male; D011187:Posture / Q000502:physiology*; D011412:Propanolamines / Q000009:adverse effects; D012008:Recurrence; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013375:Substance Withdrawal Syndrome; D013575:Syncope / Q000139:chemically induced / Q000209:etiology* / Q000628:therapy
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D007545:Isoproterenol; C036604:esmolol