402 JACC Vol. 19, No. 2 February 1992:402-8 REPORTS ON THERAPY Use of Intravenous Esmolol to Predict Efficacy of Oral Beta­ Adrenergic Blocker Therapy in Patients With Neurocardiogenic Syncope JASBIR S. SRA, MD, VISHNUBHAKTA S. MURTHY, MD, PHD, MOHAMMAD R. JAZAYERI, MD, FACC, YUE-HUA SHEN, MD, PAUL J. TROUP, MD, FACC, BOAZ AVITALL, MD, PHD, MASOOD AKHTAR, MD, FACC Milwaukee, Wisconsin The usefulness of esmolol in predicting the efficacy of treatment Irrespective of their response to esmolol infusion, all patients with an oral beta-adrenergic blocking agent was evaluated in 27 had a follow-up tilt test with oral metoprolol after an interval of consecutive patients with neurocardiogenic syncope. Seventeen ~5 half-lives of the drug. All 16 patients (100%) with a negative patients had a positive head-up tilt test response at baseline and 10 tilt test response during esmolol infusion had a negative tilt test patients required intravenous isoproterenol for provocation of response with oral metoprolol. Of the 11 patients with a positive hypotension. All patients were then given a continuous esmolol tilt test response during esmolol infusion, 10 (90%) continued to infusion (500 JLg/kg per min loading dose for 3 min followed by have a positive response with oral metoprolol. 300 Jlg/kg per min maintenance dose) and rechallenged with a It is concluded that in the electrophysiology laboratory, es­ head-up tilt test at baseline or with isoproterenol. molol can accurately predict the outcome of a head-up tilt Of the 17 patients with a positive baseline tilt test response, 11 response to oral metoprolol. This information may be helpful in continued to have a positive response to esmolol challenge. Sixteen formulating a therapeutic strategy at the initial head-up tilt test in patients (including all10 patients with a positive tilt test response patients with neurocardiogenic syncope. with isoproterenol) exhibited a negative response to upright tilt (JAm Coli Cardio/1992;19:402-8) during esmolol infusion. Syncope, defined as transient loss of consciousness, is Methods responsible for up to of emergency room visits in the 3% all Study patients. Twenty-seven consecutive patients (18 United States (1). Because of the intermittent and episodic female and 9 male, 12 to 75 years of age) were included in nature of syncope, a definitive etiology is difficult to docu­ this study. All patients were referred for evaluation of ment and the use of noninvasive techniques is frequently unexplained syncope and had a positive head-up tilt test unrewarding (2). Recently, the head-up tilt test alone or with isoproterenol challenge has been used as a diagnostic response at baseline study (17 patients) or after intravenous method in a subset of patients with unexplained syncope administration of isoproterenol (10 patients). Twenty-six (3-6). In these patients, neurocardiogenic mechanisms seem patients had two or more episodes and one patient had one to be the underlying cause of syncope that may respond to episode of syncope in the preceding year. In addition, 20 treatment with an oral beta-adrenergic blocking agent (7). patients had a history of recurrent presyncope. Comprehen­ The future efficacy of such agents in patients with neuro­ sive physical examination, neurologic evaluation, surface cardiogenic syncope is difficult to predict at the initial tilt electrocardiogram (ECG) and electrophysiologic evaluation test. This study was designed to determine if intravenous did not identify the cause of syncope in any of these patients. esmolol, an ultrashort-acting cardioselective beta-blocker, Two patients had coronary artery disease. The mean ejec­ would help in assessing the response of patients with neuro­ tion fraction was 63.2% (range 45% to 73%). cardiogenic syncope to long-term oral beta-blocker therapy. Head-up tilt test. During the head-up tilt test, arterial blood pressure was monitored by means of an intraarterial cannula inserted percutaneously into the brachial or femoral artery. Each patient was tilted to 70° for a maximum of From Sinai Samaritan Medical Center, Milwaukee, Wisconsin. This study was presented in part at the 63rd Annual Scientific Session of the American 15 min. If the baseline tilt test response was negative, the Heart Association, Dallas, Texas, November 1990. patient was returned to the supine position and intravenous Manuscript received April30, 1991; revised manuscript received June 19, isoproterenol infusion was started at 1 JLg/min. The infusion 1991, accepted July 12, 1991. Address for reprints: Jasbir S. Sra, MD, Sinai-Samaritan Medical Center, rate was gradually increased until a 20% increase in heart 950 North 12th Street, P.O. Box 342, Milwaukee, Wisconsin 53201. rate was achieved and the head-up tilt test was repeated. ©1992 by the American College of Cardiology 0735-1097/92/$5.00 JACC Vol. 19, No. 2 SRA ET AL. 403 February 1992:402-8 ESMOLOL IN NEUROCARDIOGENIC SYNCOPE Table 1. Clinical and Electrophysiologic Characteristics of 27 Patients Syncope Results of HUT Pt Age (yr)/ Heart Provocation No. Gender Disease (min to provocation) Esmolol Metoprolol 58/M NSHD HUT (10) 2 40/F NSHD HUT (15) 3 40/M NSHD HUT (6) 4 33/F NSHD HUT (7) 5 15/F NSHD HUT (14) 6 75/F NSHD HUT(S) 7 58/F NSHD HUT and Iso (8) 8 73/F NSHD HUT and Iso (14) 9 37/F NSHD HUT and Iso (6.5) 10 40/F NSHD HUT and Iso (6) 11 12/M NSHD HUT and lso (5 .5) 12 35/F NSHD HUT and lso (9) 13 71/F NSHD HUT and lso (3) 14 43/M NSHD HUT and lso (6.5) 15 38/F NSHD HUT and lso (3 .5) 16 38/F NSHD HUT and Iso (8) 17 34/F NSHD HUT(6) + 18 39/F NSHD HUT(6.5) + + 19 55/M NSHD HUT(6) + + 20 42/M NSHD HUT(3) + + 21 20/M NSHD HUT(2) + + 22 22/F NSHD HUT (10) + + 23 72/F CAD HUT(7) + + 24 71/F NSHD HUT (10) + + 25 43/M NSHD HUT(5) + + 26 63/M CAD HUT(7) + + 27 54/F NSHD HUT(3) + + CAD = coronary artery disease; F = female; HUT = head-up tilt test; Iso = isoproterenol; M = male; NSHD = no structural heart disease; Pt = patient; - = negative head-up tilt test response; + = positive tilt test response. A response was considered positive if significant arterial lenged with head-up tilt alone or with isoproterenol as hypotension in association with syncope or presyncope was before. All patients, irrespective of the results with esmolol, encountered. All patients with a positive tilt test response were then started on treatment with oral metoprolol. then received an infusion of esmolol at 500 p.g/kg for 3 min Twenty-six patients received metoprolol, 50 mg twice daily, followed by a maintenance dose of 300 JLg/kg per min. Five and one patient who weighed 46 kg received 25 mg twice minutes after the start of the infusion, patients were rechal- daily. After ;;::5 half-lives of the drug, the head-up tilt test Figure 1. Mean arterial pressure at initi­ 150 p=NS 150 p<0.00001 150 p<0.004 ation (lnit.) and termination (Term.) of LLI tilt test at baseline tilt (left IX the head-up 125 panel), during esmolol infusion (middle ~ 125 125 Cl) panel) and with oral metoprolol (right LLI panel) in 16 patients who demonstrated a 100 100 f.-. ±11 ±13 negative response to the head-up tilt test ..JOI "l~I .. '" during esmolol challenge. The slight de­ ~ ~ 75 75 75 crease in arterial pressure during esmolol ffie 58 infusion is insignificant as compared with 1-"- I± 12 a: 50 50 50 the baseline level. Furthermore, none of o( the patients had syncope or presyncope z and in no patient was the decrease in ~ 25 25 25 arterial pressure during esmolol chal­ :& 0 ..._ ...__ .... _ lenge > 13 mm Hg. Similarly, arterial 0 0 pressure changes with metoprolol were I nit. Term. I nit. Term. lnit. Term. insignificant in comparison with the level BASELINE ESMOLOL METOPROLOL during baseline tilt. 404 SRA ET AL. JACC Vol. 19, No. 2 ESMOLOL IN NEUROCARDIOGENIC SYNCOPE February 1992:402-8 180 p<0.0007 180 p<0.03 180 p=NS 160 160 160 - 140 140 140 E Figure 2. Heart rate changes in the 16 pa­ .8' 120 120 tients who had a negative head-up tilt re­ sponse during esmolol infusion. A signifi­ 100 Ill 100 cant decrease in heart rate was seen at 1- I±18.. c baseline tilt, with one patient having asys­ a: 80 ±17MI 80 t: tole. In comparison, a minimal increase or c 60 60 no significant change was seen when the Ill same patients were rechallenged with a :t: 40 40 40 head-up tilt test during esmolol infusion and subsequently with oral metoprolol. Format 20 20 20 and abbreviations as in Figure 1. 0 0 0 I nit. Term. I nit. Term. lnlt. Term. BASELINE ESMOLOL METOPROLOL was repeated under similar circumstances as before (that is, 15). The mean time to a positive head-up tilt test with at baseline study or after intravenous isoproterenol). isoproterenol provocation was 6.8 ± 3.2 min (range 2 to 15). Statistical analysis. The data are expressed as mean val­ Patients with a negative head-up tilt test response during ues ± SD. Paired and unpaired t test analysis was used to esmolol infusion. Changes in mean arterial pressure and compare heart rate and blood pressure within the same heart rate during the head-up tilt test at baseline, during group and between different groups. A p value < 0.05 was esmolol infusion and during oral metoprolol therapy are considered significant.