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clinical practice
Neurocardiogenic Syncope
Blair P. Grubb, M.D.
This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the author’s clinical recommendations.
A 23-year-old nurse presents for evaluation after having had five episodes of syncope
at work during the previous three months. All the episodes occurred while she was
standing and were characterized by a feeling of light-headedness lasting one to two
seconds and then an abrupt loss of consciousness. Two of the episodes caused falls
that resulted in facial trauma. The syncope was brief and not associated with inconti-
nence; it was followed by severe fatigue but no confusion. How should the patient be
evaluated and treated?
* This treatment has been reported to be effective in at least one randomized clinical trial. For beta-blockers, other ran-
domized clinical trials showed no benefit.
† Recent well-controlled randomized trials showed no benefit. DDD denotes dual-chamber cardiac pacing.
shown that these agents may reduce recurrent neu- Given the lack of consistent data from random-
rocardiogenic syncope.41,42 In a randomized place- ized trials to support its use and the potential com-
bo-controlled trial, 82 percent of the patients who plications, pacing is not recommended as first-line
were randomly assigned to receive paroxetine were therapy. However, it may have a role for some pa-
free of syncope for 25 months, as compared with tients, specifically those who have little or no pro-
53 percent of the placebo group (P<0.001).43 drome, those in whom other forms of therapy fail,
and those who have profound bradycardia or asys-
other therapies tole during syncope. For such patients, cardiac pac-
Transdermal scopolamine was not superior to pla- ing may increase the amount of time from the onset
cebo in a randomized trial involving 60 patients with of symptoms to a loss of consciousness,52 thereby
neurocardiogenic syncope.44 Controlled studies are providing time for the patient to take evasive action
needed to support the use of several other proposed (i.e., lie down).
agents, including disopyramide, enalapril, theo-
phylline, and ephedrine.24,32 guidelines
In uncontrolled studies involving patients in
whom emotional stimuli such as the sight of blood Guidelines on the evaluation of syncope have been
or a needle provoke syncope, biofeedback has been issued by the American College of Physicians,3 the
effective in “desensitizing” the person to the psy- Heart Rhythm Society (formerly called the North
chological stressor and reducing the risk of recur- American Society of Pacing and Electrophysiolo-
rent syncope.45,46 gy),4 the American College of Cardiology,13 and the
European Society of Cardiology14 — guidelines that
cardiac pacing are consistent with the approach discussed here.
The implantation of a permanent dual-chamber The European Society of Cardiology has also issued
pacemaker has been proposed for patients with re- treatment guidelines,14 but these do not recom-
current neurocardiogenic syncope that is refractory mend any particular medication; the recommenda-
to other therapies, on the basis of the observation tions regarding pacing antedated the recent nega-
that roughly one third of patients have substantial tive results of controlled trials.
bradycardia or asystole during tilt-induced and
spontaneously recorded syncope.47 Initial random- areas of uncertainty
ized trials showed that the pacemaker was effective
in preventing syncope.48 However, since subjects The pathophysiology of neurocardiogenic syncope
were randomly assigned to receive a pacemaker, remains uncertain. There are few data available on
there was concern that the observed benefit might the natural history of this disorder, and the results
reflect a placebo effect.49 of a few large randomized trials guide decision mak-
In two subsequent trials, pacemakers were im- ing regarding the optimal therapy. The appropriate
planted in all subjects, who were then randomly as- role for implantable loop recorders in the diagnos-
signed to have the pacemaker turned on or off.50,51 tic evaluation of syncope is still being defined.
The Vasovagal Pacemaker Study II showed no sig-
nificant reduction in the time to a first recurrence summary and recommendations
of syncope with dual-chamber pacing during six
months of follow-up (relative risk reduction, 30 per- In the case of a patient presenting with syncope, a
cent; 95 percent confidence interval, ¡33 to 63 per- detailed history (with attention to any personal or
cent).50 Complications included one case each of family history of cardiac disease or associated symp-
venous thrombosis, pericardial tamponade, and in- toms and possible precipitants) and a physical ex-
fection. Preliminary results of the Vasovagal Synco- amination (particularly for signs of cardiac disease)
pe and Pacing Trial51 showed no significant differ- are often sufficient to categorize the event with a
ence in the frequency of syncope between the group high likelihood as neurocardiogenic. To rule out
with pacing and that without pacing, although the cardiovascular disease more definitively, I routinely
subgroup of patients who had asystole in response obtain an electrocardiogram (looking for abnor-
to a tilt-table test at baseline had a significantly long- malities such as the long-QT syndrome or bundle-
er time to a first recurrence of syncope with pacing branch block).
than did patients in the subgroup without pacing. In a case such as the one described in the vi-
gnette, given the severe episodes of syncope (with and in which episodes have been associated with
minimal prodrome and associated with injury), I physical injury, such as that of the patient described,
would recommend additional evaluation, including I would also start prophylactic medication. I would
an echocardiogram (to rule out structural heart dis- first try midodrine at 5 mg orally three times daily
ease) and tilt-table testing to provide reassurance (because of its rapid onset of action) and then in-
that these episodes were caused by neurocardio- crease the dose to 10 mg orally three times daily if
genic syncope, even while recognizing that a false syncope or near-syncope recurred.53 If episodes
positive test is possible. were reduced in severity and frequency but were still
The first line of therapy for neurocardiogenic occurring, I would consider the addition of fludro-
syncope is education regarding adequate salt and cortisone at 0.1 mg orally daily (even though sup-
fluid intake (roughly 2 liters a day of fluid) and, if porting data from randomized trials are lacking) or
prodromal symptoms occur, physical maneuvers the use of a selective serotonin-reuptake inhibitor
such as gripping of the hands and tensing of the (on the basis of limited data from clinical trials).
arms and legs. Although the value of “tilt training” Although data are lacking on the optimal duration
is controversial, I would recommend that the pa- of therapy, I would taper and ultimately discontinue
tient stand for a short period each day with her back medication if the patient remained asymptomatic
against a wall, starting with 5 minutes of standing on treatment for one year (an arbitrary end point)
and increasing to 15 to 30 minutes a day. but would follow the patient and reinitiate medi-
In cases in which there is little or no prodrome, cation if her symptoms recurred.
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