Europace (2009) 11, 562–564 REVIEW

doi:10.1093/europace/eup014

Treatment of persistent sinus bradycardia with

intermittent symptoms: are guidelines clear?
Paolo Alboni 1*, Lorella Gianfranchi1, and Michele Brignole 2
1
Division of Cardiology, Arrhythmologic Center, Ospedale Civile di Cento, 44042 Cento (FE), Italy; and 2Department of Cardiology, Arrhythmologic Center, Ospedali del Tigullio,
Lavagna, Italy

Received 15 October 2008; accepted after revision 14 January 2009; online publish-ahead-of-print 12 February 2009

There is uncertainty in the aetiology of syncope in subjects with persistent sinus bradycardia (SB) (sick sinus syndrome). The results of patho-
physiological studies suggest a reflex origin of syncope in the vast majority of subjects with SB. From a nosological point of view, ‘syndrome’ is
defined as the association of signs and symptoms that have a pathophysiological correlation. Since in most cases the causal relationship
between syncope and persistent SB appears very weak, ‘reflex syncope with associated SB’ appears to be the most appropriate diagnosis.
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Keywords Carotid sinus massage † Sick sinus syndrome † Sinus bradycardia † Syncope † Tilt testing

The sick sinus syndrome is a descriptive term that refers to a con-
stellation of signs and symptoms defining sinus node dysfunction in
a clinical setting. The most frequent electrocardiographic (ECG)
sign is persistent sinus bradycardia (SB), (sinus rate , 50 bpm).
Although persistent clinical manifestations of bradycardia (due to
the consequent reduction in cerebral and peripheral perfusion)
such as subtle symptoms of fatigue, irritability, lassitude, inability
to concentrate, lack of interest, forgetfulness, and dizziness can
be expected, it is more difficult to explain intermittent symptoms
(syncope and pre-syncope), which are present in about a half of
the patients affected by sinus node dysfunction requiring hospital
assistance.1,2 Although persistent symptomatic bradycardia clearly
defines sick sinus syndrome, the meaning of intermittent severe
SB or sinus arrest is less clear. Indeed, the same event (i.e. intermit-
tent symptomatic sinus arrest) may be diagnosed by one physician
as sick sinus syndrome and by another as cardio-inhibitory reflex
syndrome. On the other hand, the same syncope may be diag-
nosed as reflex if not documented, whereas it may be diagnosed
as sick sinus syndrome if there is fortuitous documentation of a
pause.
This uncertainty of the aetiology of syncope in subjects with SB
is also reflected in the recommendations for pacing therapy of the
European3 and American guidelines.4 Indeed, in the European
guidelines ‘Syncope with sinus node disease . . . .spontaneously
occurring . . . ’ is considered among class I indications, and in the
American guidelines, ‘Syncope of unexplained origin when clinically
significant abnormalities of sinus node function . . . ’ is considered
among class IIa indications. These definitions seem to overlap
with those used in the same guidelines for neurally mediated
syncope. Indeed, in the European guidelines, ‘Recurrent severe
vasovagal syncope in patients who show prolonged asystole
during ECG recording’ is a class IIa indication, and in the American
guidelines, ‘Significantly symptomatic neurocardiogenic syncope
associated with bradycardia documented spontaneously’ is a class
IIb indication.
Pathophysiology of syncope in
subjects with sinus bradicardia
The possible role of autonomic factors in the genesis of signs and
symptoms characterizing sick sinus syndrome has been suggested
for a long time.
Two studies5,6 have specifically evaluated the relationship
between syncope and abnormal reflexes in patients with SB.
Brignole et al. 5 performed head-up tilt testing (HUT) and carotid
sinus massage (CSM) with the method of symptoms in 35 patients
with SB and syncope and compared the results with those
obtained in 35 patients with normal sinus rate who were affected
by syncope of uncertain origin. The percentage of positive HUT in
the subjects with SB was high (54%): higher than that recorded in
the subjects with syncope of uncertain origin (26%). The percen-
tage of positive CSM in the subjects with SB was also high (60%)
and similar to that observed in patients with syncope of uncertain
origin (63%). Thus, an abnormal neural reflex played a major role
in causing syncope in subjects with SB. In order to evaluate

* Corresponding author. Tel: þ39 51 6838219, Fax: þ39 51 6838471, Email: p.alboni@ausl.fe.it
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

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 Treatment of persistent SB with intermittent symptoms
whether a sinus node dysfunction could enhance the
cardio-inhibitory efferent reflex response, and therefore predis-
pose patients to positivity in these tests, Alboni et al. 6 studied
two groups of subjects with SB, one with history of syncope and
one without. The clinical characteristics, Holter monitoring data,
and basal and intrinsic corrected sinus node recovery time
(CSNRT) were similar in the two groups. The patients with SB
and syncope had a higher prevalence of positive response to
HUT (60 vs. 12%, P ¼ 0.001) and CSM (44 vs. 22%, not significant)
than those without syncope; overall, 76% of the patients with
syncope had at least one positive test vs. 36% of those without
syncope (P ¼ 0.01). Moreover, positivity to these tests was inde-
pendent of the presence of intrinsic sinus node dysfunction and
the severity of SB. The results of these two studies suggest that,
in subjects with SB, syncope is mainly related to an abnormal
neural reflex and that the diseased sinus node may play a marginal
facilitating role in the development of a cardio-inhibitory reflex,
with the possible exception of the minority of patients with a
very prolonged CSNRT suggestive of a major depression of sinus
node automaticity.7 In other words, these results suggest that
when in the general population an asymptomatic subject with SB
experiences a neurally mediated syncope, he/she becomes a sick
sinus syndrome patient.
A reflex mechanism of syncope fits well with the unpredictable
natural history of syncopal recurrences (only 46% recurrence rate
in non-treated patients during 4-year follow-up)2 – 7 and can explain
why neurological symptoms have no prognostic relevance in sub-
jects with sinus node dysfunction.8 However, another possible
mechanism of syncope must be considered, that is, a prolonged
pause following the termination of atrial tachyarrhythmias in
patients with brady–tachy syndrome. We do not know the preva-
lence of this mechanism of syncope and a prospective study utiliz-
ing the implantable loop recorder should be carried out, but the
above-mentioned data suggest that a reflex mechanism should be
more frequent.
Syncope and sinus bradycardia:
what is the diagnosis?
From a nosological point of view, ‘syndrome’ is defined as the
association of signs and symptoms that have a pathophysiological
correlation. Both signs and symptoms are necessary to define a
syndrome. Thus, ‘sick sinus syndrome’ should be defined only
when symptoms are clearly correlated with a severe bradycardia/
asystole secondary to a diseased sinus node (cause –effect relation-
ship). In bradycardic patients in whom syncope is the only
symptom, a diagnosis of sick sinus syndrome can be made in a min-
ority of patients who show: (i) ECG documentation of prolonged
pause/s following the termination of a tachycardia or (ii) prolonged
CSNRT (.800 ms).3,7 In the other cases, the causal relationship
between syncope and persistent SB is very weak, and bradycardia
might be an unrelated comorbidity accompanying a reflex syncope.
In these cases, especially if HUT and CSM are abnormal, the most
appropriate diagnosis appears to be ‘reflex syncope with associ-
ated SB’.
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563
Practical implications
Distinguishing sick sinus syndrome from reflex syncope with associated
SB has a practical value in the selection of candidates for cardiac
pacing. While cardiac pacing is an effective therapy in sick sinus syn-
drome,2 its value is more questionable in the latter cases.
From a practical point of view, subjects with SB and syncope,
without other symptoms attributable to sinus node dysfunction,
should undergo autonomic tests (HUT potentiated with nitrogly-
cerin and CSM with the method of symptoms) and electrophysio-
logical study in order to assess, as far as possible, the mechanism of
syncope. In the presence of depressed sinus node automaticity
(CSNRT . 800 ms), pacemaker implantation appears indicated. If
the CSNRT is not prolonged and the HUT is positive, we should
consider that the mechanism of reflex syncope is heterogeneous,
with severe bradycardia or asystole accounting for only about
half of the syncopal events, while a dominant vasodepressor
reflex is the likely mechanism in the other cases.9 While cardiac
pacing could be effective when an asystole is documented at the
time of syncope, there is no rationale for the use of pacing in
patients with dominant vasodepressive syncope. Likely for this
reason, controlled trials of tilt-guided therapy have often failed
to show a benefit, and evidence of the efficacy of empirical
therapy for reflex syncope is weak.10,11
The recognition of an important vasodepressor reflex makes
pacing therapy questionable. On the other hand, cardiac pacing
is likely to be effective in reflex syncopes when a prolonged asys-
tolic reflex is documented during a spontaneous syncope.9 There-
fore, also in patients with reflex syncope with associated SB, without
other symptoms attributable to persistent SB, an attempt to docu-
ment a spontaneous event should be made before embarking upon
permanent cardiac pacing. In any case, it must be underlined that
the decision to implant a pacemaker needs to be kept in the clinical
context of a benign condition,8 the intention being to avoid
intermittent symptoms and not to treat an otherwise asympto-
matic SB.
Making guidelines more clear
In the present guidelines, the clinical situation of persistent SB with
intermittent symptoms is discussed both in the sick sinus syndrome
section and in the vasovagal syncope section, but the terminology
and the recommendations are different. Therefore, they should be
unified in the section reflex syncope with associated SB. In the clinical
setting, defining a correlation between intermittent symptoms and
heart rhythm is warranted. On the basis of the present knowledge,
in subjects with asymptomatic SB and syncope, indication to pace-
maker implantation should be confined to patients with prolonged
CSNRT or with documentation of spontaneous asystole.
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