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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- with those used in the same guidelines for neurally mediated
stellation of signs and symptoms defining sinus node dysfunction in syncope. Indeed, in the European guidelines, ‘Recurrent severe
a clinical setting. The most frequent electrocardiographic (ECG) vasovagal syncope in patients who show prolonged asystole
sign is persistent sinus bradycardia (SB), (sinus rate , 50 bpm). during ECG recording’ is a class IIa indication, and in the American
Although persistent clinical manifestations of bradycardia (due to guidelines, ‘Significantly symptomatic neurocardiogenic syncope
the consequent reduction in cerebral and peripheral perfusion) associated with bradycardia documented spontaneously’ is a class
such as subtle symptoms of fatigue, irritability, lassitude, inability IIb indication.
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 Pathophysiology of syncope in
the patients affected by sinus node dysfunction requiring hospital
assistance.1,2 Although persistent symptomatic bradycardia clearly
subjects with sinus bradicardia
defines sick sinus syndrome, the meaning of intermittent severe The possible role of autonomic factors in the genesis of signs and
SB or sinus arrest is less clear. Indeed, the same event (i.e. intermit- symptoms characterizing sick sinus syndrome has been suggested
tent symptomatic sinus arrest) may be diagnosed by one physician for a long time.
as sick sinus syndrome and by another as cardio-inhibitory reflex Two studies5,6 have specifically evaluated the relationship
syndrome. On the other hand, the same syncope may be diag- between syncope and abnormal reflexes in patients with SB.
nosed as reflex if not documented, whereas it may be diagnosed Brignole et al. 5 performed head-up tilt testing (HUT) and carotid
as sick sinus syndrome if there is fortuitous documentation of a sinus massage (CSM) with the method of symptoms in 35 patients
pause. with SB and syncope and compared the results with those
This uncertainty of the aetiology of syncope in subjects with SB obtained in 35 patients with normal sinus rate who were affected
is also reflected in the recommendations for pacing therapy of the by syncope of uncertain origin. The percentage of positive HUT in
European3 and American guidelines.4 Indeed, in the European the subjects with SB was high (54%): higher than that recorded in
guidelines ‘Syncope with sinus node disease . . . .spontaneously the subjects with syncope of uncertain origin (26%). The percen-
occurring . . . ’ is considered among class I indications, and in the tage of positive CSM in the subjects with SB was also high (60%)
American guidelines, ‘Syncope of unexplained origin when clinically and similar to that observed in patients with syncope of uncertain
significant abnormalities of sinus node function . . . ’ is considered origin (63%). Thus, an abnormal neural reflex played a major role
among class IIa indications. These definitions seem to overlap 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 563

whether a sinus node dysfunction could enhance the Practical implications


cardio-inhibitory efferent reflex response, and therefore predis-
pose patients to positivity in these tests, Alboni et al. 6 studied Distinguishing sick sinus syndrome from reflex syncope with associated
two groups of subjects with SB, one with history of syncope and SB has a practical value in the selection of candidates for cardiac
one without. The clinical characteristics, Holter monitoring data, pacing. While cardiac pacing is an effective therapy in sick sinus syn-
and basal and intrinsic corrected sinus node recovery time drome,2 its value is more questionable in the latter cases.
(CSNRT) were similar in the two groups. The patients with SB From a practical point of view, subjects with SB and syncope,
and syncope had a higher prevalence of positive response to without other symptoms attributable to sinus node dysfunction,
HUT (60 vs. 12%, P ¼ 0.001) and CSM (44 vs. 22%, not significant) should undergo autonomic tests (HUT potentiated with nitrogly-
than those without syncope; overall, 76% of the patients with cerin and CSM with the method of symptoms) and electrophysio-
syncope had at least one positive test vs. 36% of those without logical study in order to assess, as far as possible, the mechanism of
syncope (P ¼ 0.01). Moreover, positivity to these tests was inde- syncope. In the presence of depressed sinus node automaticity
pendent of the presence of intrinsic sinus node dysfunction and (CSNRT . 800 ms), pacemaker implantation appears indicated. If
the severity of SB. The results of these two studies suggest that, the CSNRT is not prolonged and the HUT is positive, we should
in subjects with SB, syncope is mainly related to an abnormal consider that the mechanism of reflex syncope is heterogeneous,
neural reflex and that the diseased sinus node may play a marginal with severe bradycardia or asystole accounting for only about
facilitating role in the development of a cardio-inhibitory reflex, half of the syncopal events, while a dominant vasodepressor
with the possible exception of the minority of patients with a reflex is the likely mechanism in the other cases.9 While cardiac
very prolonged CSNRT suggestive of a major depression of sinus pacing could be effective when an asystole is documented at the
node automaticity.7 In other words, these results suggest that time of syncope, there is no rationale for the use of pacing in
when in the general population an asymptomatic subject with SB patients with dominant vasodepressive syncope. Likely for this
experiences a neurally mediated syncope, he/she becomes a sick reason, controlled trials of tilt-guided therapy have often failed
sinus syndrome patient. to show a benefit, and evidence of the efficacy of empirical
A reflex mechanism of syncope fits well with the unpredictable therapy for reflex syncope is weak.10,11
natural history of syncopal recurrences (only 46% recurrence rate The recognition of an important vasodepressor reflex makes
in non-treated patients during 4-year follow-up)2 – 7 and can explain pacing therapy questionable. On the other hand, cardiac pacing
why neurological symptoms have no prognostic relevance in sub- is likely to be effective in reflex syncopes when a prolonged asys-
jects with sinus node dysfunction.8 However, another possible tolic reflex is documented during a spontaneous syncope.9 There-
mechanism of syncope must be considered, that is, a prolonged fore, also in patients with reflex syncope with associated SB, without
pause following the termination of atrial tachyarrhythmias in other symptoms attributable to persistent SB, an attempt to docu-
patients with brady–tachy syndrome. We do not know the preva- ment a spontaneous event should be made before embarking upon
lence of this mechanism of syncope and a prospective study utiliz- permanent cardiac pacing. In any case, it must be underlined that
ing the implantable loop recorder should be carried out, but the the decision to implant a pacemaker needs to be kept in the clinical
above-mentioned data suggest that a reflex mechanism should be context of a benign condition,8 the intention being to avoid
more frequent. intermittent symptoms and not to treat an otherwise asympto-
matic SB.

Making guidelines more clear


Syncope and sinus bradycardia:
In the present guidelines, the clinical situation of persistent SB with
what is the diagnosis? intermittent symptoms is discussed both in the sick sinus syndrome
From a nosological point of view, ‘syndrome’ is defined as the section and in the vasovagal syncope section, but the terminology
association of signs and symptoms that have a pathophysiological and the recommendations are different. Therefore, they should be
correlation. Both signs and symptoms are necessary to define a unified in the section reflex syncope with associated SB. In the clinical
syndrome. Thus, ‘sick sinus syndrome’ should be defined only setting, defining a correlation between intermittent symptoms and
when symptoms are clearly correlated with a severe bradycardia/ heart rhythm is warranted. On the basis of the present knowledge,
asystole secondary to a diseased sinus node (cause –effect relation- in subjects with asymptomatic SB and syncope, indication to pace-
ship). In bradycardic patients in whom syncope is the only maker implantation should be confined to patients with prolonged
symptom, a diagnosis of sick sinus syndrome can be made in a min- CSNRT or with documentation of spontaneous asystole.
ority of patients who show: (i) ECG documentation of prolonged
pause/s following the termination of a tachycardia or (ii) prolonged References
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564 P. Alboni et al.

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