Correspondence
Treatment of Neurocardiogenic Syncope
N Engl J Med 1993; 329:969-970September 23, 1993
- Article
To the Editor:
Sra et al. (April 15 issue)1 found that in patients with neurocardiogenic syncope associated with bradycardia or asystole, drug therapy is often effective in preventing syncope, whereas artificial pacing is not. This study raises important questions about the methods used to diagnose vasovagal responses and evaluate treatment. The reported mean time of seven minutes from the onset of tilt testing to syncope is extremely short. We suggest that the heavily invasive instrumentation used in the study contributed to both the incidence and the early onset of syncope. Intravascular instrumentation has been shown to raise the incidence of vasovagal fainting fivefold2 to 50 to 90 percent during prolonged tilting in healthy subjects who have no history of fainting2-4. This is even more important when one takes into account that Sra et al. evaluated the effects of pharmacologic treatment (reduction of the incidence of syncope) under different test conditions -- i.e., head-up tilt testing in the absence of intravascular instrumentation. Head-up tilt testing in combination with invasive instrumentation appears to result in a nonspecific test in young and adult subjects, as was shown previously for tilting in combination with isoproterenol. In this regard, the recent development of noninvasive continuous tracking of finger arterial pressure promises to be of advantage3. The age of the subject, the use or nonuse of intravascular instrumentation, the administration of isoproterenol, the duration of tilting, and the degree of familiarity with the protocol should all be considered in the interpretation of a positive tilt test.
4 ReferencesJohannes J. van Lieshout, M.D., Ph.D.
Wilbert T. Jellema, M.Sc.
Wouter Wieling, M.D., Ph.D.
Academic Medical Center, 1105 AZ Amsterdam, the Netherlands1
Sra JS ,Jazayeri MR ,Avitall B , et al. Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole. N Engl J Med 1993;328:1085-1090
Full Text | Web of Science | Medline2
Stevens PM . Cardiovascular dynamics during orthostasis and the influence of intravascular instrumentation. Am J Cardiol 1966;17:211-218
CrossRef | Web of Science | Medline3
Imholz BP ,Wieling W ,Langewouters GJ ,van Montfrans GA . Continuous finger arterial pressure: utility in the cardiovascular laboratory. Clin Auton Res 1991;1:43-53
CrossRef | Medline4
van Lieshout JJ ,Wieling W ,Karemaker JM ,Eckberg DL . The vasovagal response. Clin Sci 1991;81:575-586
Web of Science | Medline
To the Editor:
Sra et al. state that “No studies have yet demonstrated the efficacy of cardiac pacing . . . in preventing hypotension and syncope” in patients with neurocardiogenic syncope. This statement is not correct. In one controlled laboratory study using hysteresis temporary dual-chamber pacing during serial invasive tilt tests on consecutive days,1 syncope produced in seven patients on the first day was prevented in six of these patients by dual-chamber pacing on the second day. Pacing significantly increased the mean arterial blood pressure and cardiac index in patients with vasovagal reactions of identical severity. Vasovagal symptoms still occurred, however, and the vasovagal attack was only ameliorated by pacing. The investigators concluded that pacing was not a panacea for vasovagal syncope, but that the improvement shown might allow the patient time to take evasive action at the onset of a vasovagal attack and avoid injury. This small but demonstrated benefit might in some cases be considered preferable to the inconvenience, expense, and side effects of lifelong daily medication for attacks that, characteristically, occur very infrequently.
The results of pacing in the study of Sra et al. are remarkably similar, but their interpretation is different. They conclude that “drug therapy is often effective in preventing syncope, whereas artificial pacing is not,” but this is not shown. At base-line tilt testing, 18 of 21 patients had syncope (loss of consciousness, according to the authors' definition). During dual-chamber pacing, however, only 5 patients had syncope and 15 had presyncope, results closely mirroring those of the earlier study.
In contrast to the interpretation given to these findings, the uncontrolled findings of miscellaneous drug therapy are promoted. To date, only two placebo-controlled studies of medical therapy for tilt-induced syncope have been reported, and neither has shown any benefit of such therapy over placebo. In one randomized, crossover, placebo-controlled, double-dummy study of three drugs (atenolol, scopolamine, and clonidine) in 13 patients,2 there were fewer positive repeat tilt tests with scopolamine (6 patients) or clonidine (6) than with atenolol (8 patients) or placebo (9) (P not significant), but the mean time tolerated in the tilted position was significantly less with atenolol (19 ±7 minutes) than with placebo (26 ±8 minutes), scopolamine (37 ±8 minutes), or clonidine (33 ±9 minutes) (P<0.05).
In another recent study3 disopyramide was compared with placebo in patients with positive tilt tests. The proportion of positive repeat tests with intravenous disopyramide and oral disopyramide was no different from the result with placebo. In addition to giving data on uncontrolled drug treatment, Sra et al. make no mention of the imperfect reproducibility of the test documented elsewhere,4 which might explain any of the observed responses to unblinded treatment. The conclusion of Abboud in his editorial in the same issue5 -- “a placebo is always needed to allow for variables that may influence the reproducibility of the test” -- is appropriate. This is important to ensure that patients are not committed to lifelong medical therapy until it has proved effective in controlled trials.
5 ReferencesAdam P. Fitzpatrick, M.D., M.R.C.P.
University of California, San Francisco, San Francisco, CA 941431
Fitzpatrick A ,Theodorakis G ,Ahmed R ,Williams T ,Sutton R . Dual chamber pacing aborts vasovagal syncope induced by head-up 60 degrees tilt. Pacing Clin Electrophysiol 1991;14:13-19
CrossRef | Web of Science | Medline2
Fitzpatrick AP ,Ahmed R ,Williams S ,Travill C ,Sutton R . A randomised trial of medical therapy for vasodepressor vasovagal syncope. Eur J Cardiac Pacing Electrophysiol 1991;2:43-483
Morillo CA ,Leitch JW ,Yee R ,Klein GJ . A placebo controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt. J Am Coll Cardiol 1993;21:111A-111A abstract.4
Fitzpatrick AP ,Theodorakis G ,Vardas P ,Sutton R . Methodology of head-up tilt testing in patients with unexplained syncope. J Am Coll Cardiol 1991;17:125-130
CrossRef | Web of Science | Medline5
Abboud FM . Neurocardiogenic syncope. N Engl J Med 1993;328:1117-1120
Full Text | Web of Science | Medline
To the Editor:
As a primary care physician, it is important for me to know the patient population represented in the study by Sra et al. I can only assume that the sample represents a select group of referral patients. This information becomes even more important in the context of the limitations of tilt-table testing1 and the lack of a uniform protocol, as pointed out in the accompanying editorial2.
2 ReferencesLouis J. Papa, M.D.
St. Mary's Hospital, Rochester, NY 146111
Kapoor WN ,Brant N . Evaluation of syncope by upright tilt testing with isoproterenol: a nonspecific test. Ann Intern Med 1992;116:358-363
Web of Science | Medline2
Abboud FM . Neurocardiogenic syncope. N Engl J Med 1993;328:1117-1120
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: In response to Dr. van Lieshout et al., we disagree with the statement that the mean time of seven minutes from the beginning of tilt testing to syncope is short. This interval corresponds well to that in other reported studies1,2. Using the same approach, we have demonstrated that the specificity of the test with tilting at 70 degrees is excellent3. In a recent report from our laboratory, the use of esmolol infusion during the initial study (with similar instrumentation) and follow-up testing with oral metoprolol showed excellent reproducibility4.
In response to Dr. Fitzpatrick, our study population included patients who had severe symptoms and the most malignant presentation during head-up tilt testing. Despite artificial pacing, blood pressure fell dramatically; almost all the patients still had syncope or presyncope. In contrast, drug therapy prevented syncope and presyncope in 19 patients during head-up tilt testing and in 18 of the 19 patients (95 percent) during clinical follow-up. This correlates well with previously published data5-7. As we mentioned, double-blind studies will be needed to identify patients with neurocardiogenic syncope who may benefit from drug therapy. Furthermore, the natural history of this disorder is still unclear. Fitzpatrick and colleagues have themselves reported spontaneous remission in some patients with neurocardiogenic syncope8. Most of the patients with this disorder are relatively young. We found pacemaker therapy to be clearly inferior to drugs. In our view, it is not justified to advocate an invasive procedure such as pacemaker implantation in a young patient predominantly on the basis of assumptions. This practice should be discouraged.
8 ReferencesJasbir S. Sra, M.D.
University of Wisconsin Medical School, Milwaukee, WI 53215-36601
Abi-Samra F ,Maloney JD ,Fouad-Tarazi FM ,Castle LW . The usefulness of head-up tilt testing and hemodynamic investigations in the workup of syncope of unknown origin. Pacing Clin Electrophysiol 1988;11:1202-1214
CrossRef | Web of Science | Medline2
Almquist A ,Goldenberg IF ,Milstein S , et al. Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med 1989;320:346-351
Full Text | Web of Science | Medline3
Natale A ,Sra J ,Avitall B , et al. Specificity of head-up tilt: effects of degree of tilt and isoproterenol infusion. J Am Coll Cardiol1993;156A-156A abstract.4
Sra JS ,Murthy VS ,Jazayeri MR , et al. Use of intravenous esmolol to predict efficacy of oral beta-adrenergic blocker therapy in patients with neurocardiogenic syncope. J Am Coll Cardiol 1992;19:402-408
CrossRef | Web of Science | Medline5
Sra JS ,Anderson AJ ,Sheikh SH , et al. Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing. Ann Intern Med 1991;114:1013-1019
Web of Science | Medline6
Goldenberg IF ,Almquist A ,Dunbar DN ,Milstein S ,Pritzker MR ,Benditt DG . Prevention of neurally-mediated syncope by selective beta-1 adrenoceptor blockade. Circulation 1987;76:Suppl IV:IV-133 abstract.7
Abi-Samra FM ,Davison NM ,Gohn DC ,Vincent KA . Longterm effectiveness of beta blockers for the treatment of recurrent vasodepressor syncope. J Am Coll Cardiol 1992;19:339A-339A
CrossRef8
Fitzpatrick A ,Sutton R . Tilting towards a diagnosis in recurrent unexplained syncope. Lancet 1989;1:658-660
CrossRef | Web of Science | Medline
