PDF - Advances in Clinical and Experimental Medicine

PDF - Advances in Clinical and Experimental Medicine

original papers
Adv Clin Exp Med 2011, 20, 3, 305–312
ISSN 1230-025X
© Copyright by Wroclaw Medical University
Jacek Gajek1, Dorota Zyśko2, Anil K. Agrawal3, Jerzy Rudnicki4
Patients with Atrioventricular Block
During Tilt Test-Induced Vasovagal Syncope
Pacjenci z blokiem przedsionkowo-komorowym
podczas testu pochyleniowego
Department of Cardiology, Wroclaw Medical University, Wrocław, Poland
Department of Emergency Medicine, Wroclaw Medical University, Wrocław, Poland
3
2nd Department and Clinic of General and Oncological Surgery, Wroclaw Medical University, Wrocław,
Poland
4
Department of Minimally Invasive Surgery and Proctology, Wroclaw Medical University, Wrocław, Poland
1
2
Abstract
Background. Sinus bradycardia or sinus arrest are the most prevalent rhythms during a cardioinhibitory type of
neurocardiogenic reaction, while atrioventricular block (AVB) occurs rarely.
Objectives. The aim of the study was to compare the medical histories and tilt test (TT) findings among patients
with and without AVB during a positive TT.
Material and Methods. The study group consisted of 578 vasovagal patients with positive TTs. Among them there
were 34 patients with AVB, which constituted 5.9% of the total study group. The medical histories and TT data
were analyzed. The TTs were performed according to the Italian protocol.
Results. The medical histories of patients with AVB showed a significantly higher incidence of syncope-related
traumatic injuries requiring hospitalization. AVB occurrence was found to be independently related to a history of
instrumentation-injection-blood (IIB) phobia and to the duration of the PR interval on a baseline electrocardiogram. Receiver operating characteristic (ROC) analysis revealed that a PR interval ≤ 177 ms in duration differentiates patients without and with AVB during a neurocardiogenic reaction. It was also shown that other factors related
to AVB occurrence include a shorter duration of the slowing of the heart rate and syncope as a TT outcome.
Conclusions. Patients with AVB during TT differ from those without AVB. Sudden onset of a syncopal event,
particularly in women or in patients of either gender with instrumentation-injection-blood (IIB) phobia, can be an
indicator for AVB during vasovagal syncope. The population of subjects with AVB during TT is not homogenous;
it consists of a younger subgroup with IIB phobia, and an older subgroup with a concealed organic AV node dysfunction (Adv Clin Exp Med 2011, 20, 3, 305–312).
Key words: vasovagal syncope, tilt test, atrioventricular block.
Streszczenie
Wprowadzenie. Bradykardia zatokowa i/lub zahamowanie zatokowe są najczęstszymi rytmami podczas reakcji neurokardiogennej typu kardiodepresyjnego. Bloki przedsionkowo-komorowe wyższych stopni są obserwowane rzadko.
Cel pracy. Porównanie danych z wywiadu oraz parametrów testu pochyleniowego u pacjentów, u których podczas
reakcji neurokardiogennej wystąpił lub nie blok przedsionkowo-komorowy.
Materiał i metody. Badana grupa obejmowała 578 pacjentów z omdleniami wazowagalnymi, u których wykonano
dodatni test pochyleniowy. Wśród badanych stwierdzono występowanie kardiodepresyjnego typu reakcji neurokardiogennej w mechanizmie bloku przedsionkowo-komorowego u 34 pacjentów, co stanowiło 5,9% wszystkich
badanych. Analizie poddano dane z wywiadu od pacjentów oraz parametry testu pochyleniowego. Testy pochyleniowe wykonywano zmodyfikowanym protokołem włoskim z prowokacją NTG w razie potrzeby.
Wyniki. Wywiad chorobowy u pacjentów z blokiem przedsionkowo-komorowym wskazywał na statystycznie istotną większą częstość występowania urazów związanych z omdleniami, które wymagały hospitalizacji. Wystąpienie
bloku przedsionkowo-komorowego było niezależnie powiązane z wywiadem w kierunku omdleń na widok krwi
i instrumentację wraz z czasem trwania odstępu PR w spoczynkowym elektrokardiogramie. Analiza krzywych ROC
wykazała, że czas trwania odstępu PR ≤ 177 ms pozwalał na wyodrębnienie pacjentów z blokiem przedsionkowo-komorowym podczas reakcji neurokardiogennej. Wykazano ponadto, że innymi czynnikami wystąpienia bloku
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przedsionkowo-komorowego są krótszy czas trwania fazy zwalniania rytmu zatokowego oraz wystąpienie pełnego
omdlenia jako wyniku testu pochyleniowego.
Wnioski. Pacjenci z blokiem przedsionkowo-komorowym podczas testu pochyleniowego różnią się od osób bez
bloku. Nagły początek omdlenia, zwłaszcza u kobiet i pacjentów z omdleniami na widok krwi i instrumentację
mogą wskazywać na blok przedsionkowo-komorowy podczas omdlenia wazowagalnego. Populacja pacjentów
z blokiem przedsionkowo-komorowym podczas testu pochyleniowego nie jest jednorodna. Obejmuje osoby młodsze z omdleniami na widok krwi i instrumentację oraz starsze, najprawdopodobniej z utajonym organicznym zaburzeniem funkcji węzła przedsionkowo-komorowego (Adv Clin Exp Med 2011, 20, 3, 305–312).
Słowa kluczowe: omdlenie wazowagalne, test pochyleniowy, blok przedsionkowo-komorowy.
Sinus bradycardia or sinus arrest are the most
prevalent rhythms during a cardioinhibitory type
of neurocardiogenic reaction, and atrioventricular
block (AVB) occurs in 5% of tilt test-induced neurocardiogenic reactions [1]. Vasovagal reflexes vary
from patient to patient, and may last from a few seconds to several minutes [2]. Progressive sinus bradycardia followed by AVB with a concomitant decrease in the sinus rate is a feature of vagally induced
AVB, in contrast to a sudden onset of AVB with
a concomitant increase in the sinus rate, which is
presumed to have an intrinsic origin [3]. The slowing of the heart rate during a neurocardiogenic reaction is usually preceded by a decrease in blood pressure, but differences in the dynamics of the slowing
of the heart rate may also reflect differences in the
course of the neurocardiogenic reflex and lead to
differences in its clinical consequences.
Prodromal signs and symptoms warn fainting subjects of impending syncope, which enables
them to change their body position to prevent falls
and injuries [4, 5].
Objectives
The aim of the study was to compare the medical histories and tilt test (TT) findings among patients with and without AVB during a positive TT,
and to analyze whether patients with AVB during
a neurocardiogenic reaction are a homogenous or
heterogeneous population.
Material and Methods
The study group consisted of vasovagal patients with positive TTs. Their medical histories
were collected, focussing on the number of syncopal episodes, traumatic injuries related to syncope,
hospitalization due to such injuries, instrumentation-injections-blood (IIB) phobia, autonomic features during events and jerking movements during
spontaneous syncope.
The TT was performed according to the Italian
protocol with a 20-minute passive phase (60 de-
grees of tilt), nitroglycerine (NTG) provocation if
necessary, and continuation of the test for a further
15 minutes. Throughout the entire procedure the
subject’s ECG was recorded with the ECG Holter
monitoring system.
The procedure was carried out on an electrically controlled tilt table with a footboard for weight
bearing. Blood pressure was measured automatically using an oscillometric method. Patients were
asked to report any perception of sweating before
and after TT termination. The following TT data
were collected: the need for NTG provocation, the
duration of the slowing of the heart rate during the
neurocardiogenic reaction and the outcome of TT
assessed as a total loss of consciousness (TLOC) or
presyncope. The duration of TLOC was dichotomized and assessed as long when it lasted at least
32 seconds, or as short when it lasted no more than
31 seconds. The duration of the slowing of the
heart rate was established by analyzing the heart
rate trend line of the ECG recordings.
The patients were divided into four groups
on the basis of their TT outcomes and the cardiac rhythm during the neurocardiogenic reaction:
Group 1 had presyncope and no AVB, Group 2
had short syncope and no AVB, Group 3 had long
syncope and no AVB and Group 4 had AVB during a TT-induced neurocardiogenic reaction.
Statistical Analysis
Continuous variables are presented as means
± SD, and categorical variables as percentages and
counts. Continuous variables were compared using
a one-way ANOVA with Tukey HSD post hoc test.
Frequencies were compared with a χ2 test. A univariate logistic regression analysis was performed
to identify possible predictors for AVB occurrence.
Receiver operating characteristic (ROC) analysis
was performed to determine the cut-off points of
continuous variables that allow patients with and
without AVB to be distinguished with the highest sensitivity and specificity. Classification and
regression tree (CART) analysis was performed to
identify factors associated with AVB occurrence
during the TT-induced neurocardiogenic reaction.
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Patients with Atrioventricular Block
Predicting AVB Using Data
From Medical Histories as
Independent Variables
CART is a non-parametric method of identifying
predictor variables, described by Breiman et al. [6],
using binary recursive partitioning: CART generates a classification rule that can be visualized as
a “classification tree”. A k-means cluster analysis
assigned AVB patients to two subgroups of similar age. The parameters studied were compared in
these subgroups. All analyses were performed using Statistica and MedCalc software; and p values
< 0.05 were considered significant.
The results of the univariate analysis indicating predictors of AVB occurrence during TT are
shown in Table 3.
The multiple logistic regression analysis revealed that AVB occurrence was independently related to a history of IIB phobia and to the duration
of the PR interval on the baseline electrocardiogram. ROC analysis revealed that patients without
AVB during the neurocardiogenic reaction had PR
intervals ≤ 177 ms in duration, while those with
AVB had longer baseline PR intervals. CART analysis revealed an increased risk of AVB occurrence
among women with IIB phobia and among those
without IIB phobia whose PR interval at baseline
was longer than 177 ms. The sensitivity of this parameter was 74% and the specificity was 70%. The
results of this analysis are depicted in Fig. 1.
Results
A total of 578 patients were included in the
study. There were 34 patients with AVB (Group 4),
which constituted 5.9% of the total study population. The clinical characteristics of the patient
population are shown in Table 1 and their TT data
in Table 2.
Group 4 had a significantly higher incidence of
syncope-related traumatic injuries requiring hospitalization in their medical histories than Group 1.
Table 1. Demographics, clinical and electrocardiographic data
Tabela 1. Charakterystyka demograficzna, kliniczna oraz wskaźniki elektrokardiograficzne badanych pacjentów
Overall
without
AVB
n = 535
(Wszyscy
pacjenci
bez bloku)
Group 1
n = 146
Group 2
n = 212
Group 3
n = 177
Group 4
n = 34
Control
group
n = 47
(Grupa
kontrolna)
Age – years ± SD
(Wiek – lata ± odchylenie standardowe)
42.3 ±
17.9
42.3 ±
22.3
37.1 ±
13.9
48.6 ±
17.4
40.7 ±
18.8
38.6 ±
13.9
Male gender – %
(Płeć męska)
36
38
34
38
24
45
Syncope number median – IQ
(Liczba omdleń – mediana)
3 (1–6)
2 (0–5)
2 (1–5)
4 (2–10)
3 (1–7)
0
Traumatic injuries – % (Urazy)
30
25
26
40
32
0
Hospitalization due to trauma
(Hospitalizacja z powodu urazów)
6
3
7
8
12
0
IIB phobia – %
(Omdlewanie na widok krwi
i instrumentację)
20
14
22
23
44
0
Jerks – % (Ruchy drgawkopodobne)
5
4
4
7
15
0
Sweating – % (Pocenie się)
29
27
33
27
24
0
PR interval at baseline – ms
(Odstęp PR w spoczynku)
159 ± 28
157 ± 29
155 ± 27
167 ± 29
179 ± 38
151 ± 25
RR interval at baseline – ms
(Odstęp RR w spoczynku)
952 ± 160
942 ± 154
934 ± 134
980 ± 158
922 ± 149
944 ± 153
# – p < 0.01 vs. control group.
# – p < 0.01 vs grupa kontrolna.
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J. Gajek et al.
Table 2. Tilt testing data
Tabela 2. Test pochyleniowy
Overall
without AVB
n = 535
Group 1
n = 146
Group 2
n = 212
Group 3
n = 177
Group 4
n = 34
Control
group
n = 47
NTG use – % (Prowokacja NTG)
77
66
80
82
88
100
Syncope – % (Omdlenie)
72
0
100
100
94
0
Sweating before TT termination
(Pocenie się przed zakończeniem
testu pochyleniowego)
18
26
18
11
3
0
Sweating after TT termination
(Pocenie się po zakończeniu testu
pochyleniowego)
23
13
21
33
32
0
Duration of heart rate slowing – s
(Czas trwania spadku częstotliwości
rytmu serca)
104 ± 60
128 ± 63
96 ± 54
81 ± 56
70 ± 34
100 ± 43
Table 3. Predictors of AVB occurrence during TT in univariate analysis
Tabela 3. Czynniki predykcyjne wystąpienia bloku AV podczas testu pochyleniowego w analizie jednoczynnikowej
Odds ratio
(Iloraz szans)
95% confidence interval
(95% przedział ufności)
P-value
(Istotność statystyczna)
Age – years
(Wiek – lata)
0.69
0.17–2.79
ns.
Male gender (Płeć męska)
0.54
0.24–1.22
ns.
Syncope number (Liczba omdleń)
0.11
0.00004–318
ns.
Trauma related to syncope
(Uraz związany z omdleniem)
0.11
0.53–2.34
ns.
Hospitalisation due to trauma
(Hospitalizacja z powodu urazów)
1.96
0.65–5.91
ns.
IIB phobia (Omdlewanie na widok krwi
i instrumentację)
3.12
1.53–6.35
< 0.002
PR interval at baseline – ms
(Odstęp PR w spoczynku)
48.3
6.0–389
< 0.001
NTG use (Prowokacja NTG)
2.29
0.79–6.63
ns.
Jerks (Ruchy drgawkopodobne)
3.12
1.12–8.70
< 0.05
Syncope at TT (Omdlenie podczas testu
pochyleniowego)
6.18
1.46–26.18
< 0.02
Sweating before TT termination
(Pocenie się przed zakończeniem testu
pochyleniowego)
0.14
0.02–1.04
ns.
Sweating after TT termination
(Pocenie się po zakończeniu testu
pochyleniowego)
1.62
0.77–3.42
ns.
Duration of heart rate slowing – s
(Czas trwania spadku częstotliwości rytmu
serca)
0.003
0.0001–0.11
< 0.002
Heart rate slowing less than 72 s
(Spadek częstotliwości rytmu serca 72 s)
2.89
1.42–5.87
< 0.005
309
Patients with Atrioventricular Block
Fig. 1. The results of
CART analysis, factors
associated with AV block
occurrence during neurocardiogenic reflex, the
number 1 in the right
upper corner depicts
increased risk for AVB
occurrence
Ryc. 1. Wyniki analizy
CART, czynniki powiązane z wystąpieniem
bloku AV podczas testu
pochyleniowego, jedynka
w prawym górnym rogu
oznacza zwiększenie ryzyka bloku
Fig. 2. The results of
CART analysis, factors
associated with AV block
occurrence during neurocardiogenic reflex, the
number 1 in the right
upper corner depicts
increased risk for AVB
occurrence.
Ryc. 2. Wyniki analizy
CART, czynniki
powiązane z wystąpieniem
bloku AV podczas testu
pochyleniowego, jedynka
w prawym górnym rogu
oznacza zwiększenie
ryzyka bloku
Predicting AVB Using
TT Data as Independent
Variables
The multiple logistic regression analysis
revealed that a shorter duration of the slowing
of the heart rate and syncope as a TT outcome
are factors independently related to AVB occurrence. ROC analysis revealed that in patients
with AVB during the neurocardiogenic reaction
the slowing of the heart rate lasted under 72
seconds, which distinguished them from those
without AVB. CART analysis revealed that AVB
in female subjects with a short duration of the
slowing of the heart rate was related to a lack
of sweating before TT termination. The sensitivity of this parameter was 50% and the specificity
was 94%. The results of this analysis are depicted
in Fig. 2.
Patients with AVB
during TT
The k-means clustering analysis revealed that
the subjects with AVB constituted a heterogeneous population. Two clusters can be distinguished:
The first cluster consisted of 20 subjects aged 27.4
± 7.9 years and the second one consisted of 14 subjects aged 59.6 ± 12.0 years. A comparison of these
groups is shown in Table 4.
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J. Gajek et al.
Table 4. Comparison of AVB patients subgroups
Tabela 4. Porównanie podgrup pacjentów z blokiem AV
Group 4 a
Group 4 b
P-value
(Istotność
statystyczna)
Age – years ± SD
(Wiek – lata ± odchylenie standardowe)
27.4 ± 7.9
59.6 ± 12.0
< 0.001
Male sex – %
(Płeć męska)
10
43
< 0.001
Hypertension – % (Nadciśnienie)
0
57
< 0.001
Syncope number – median – IQ
(Liczba omdleń – mediana)
5 (2–12)
2 (1–6)
ns.
Traumatic injuries – % (Urazy)
25
42
ns.
Hospitalization due to trauma
(Hospitalizacja z powodu urazów)
5
21
ns.
IIB phobia – % (Omdlewanie na widok krwi
i instrumentację)
65
14
< 0.005
Jerking movements – % (Ruchy drgawkopodobne)
20
7
ns.
Sweating – % (Pocenie się)
20
29
ns.
PR interval at baseline ms (Odstęp PR w spoczynku)
164 ± 24
200 ± 45
< 0.01
RR interval at baseline ms (Odstęp RR w spoczynku)
897 ± 147
957 ± 149
ns.
NTG provocation – % (Prowokacja NTG)
80
100
ns.
Syncope – % (Omdlenie)
100
86
ns.
Sweating before TT termination
(Pocenie się przed zakończeniem testu pochyleniowego)
5
0
ns.
Sweating after TT termination
(Pocenie się po zakończeniu testu
pochyleniowego)
25
43
ns.
Duration of heart rate slowing – s
(Czas trwania spadku częstotliwości rytmu serca)
65 ± 29
76 ± 40
NS
Discussion
The main finding of our study is the fact that
the clinical predictors for AVB during tilt test-induced neurocardiogenic reaction are IIB phobia in
the medical history, a longer baseline PR duration
and a shorter duration of the slowing of the heart
rate. These predictors have a high sensitivity but
a low specificity.
The shorter duration of the slowing of the
heart rate during neurocardiogenic reaction in the
AVB group, as in the group with a long syncope,
may be associated with a significant decrease in the
duration of prodromal symptoms, in comparison
with the groups with presyncope and a short syncope. Assuming that this pattern during neurocardiogenic reaction persists in spontaneous events,
the clinical consequences of the shorter prodromal
phase could include an association between AVB
occurrences during TT-induced neurocardiogenic
reactions and a history of severe traumatic injuries
during spontaneous syncopal spells. A longer prodromal phase allows the subject to find a safe place
to lie down and facilitates the prevention of severe
traumatic injuries.
Our study confirmed a disparity among neurocardiogenic reactions in terms of the slowing
of the heart rate and the correlation with the
clinical courses of vasovagal reflexes assessed as
presyncope, short syncope and long syncope. The
frequency of sweating (an autonomic feature)
also varied: sweating was more frequent among
patients whose TT was terminated during presyncope. This finding indicates the importance
of sympathetic activation in the initiation of the
Patients with Atrioventricular Block
neurocardiogenic reaction as well as in the prolongation of the slowing of the heart rate. The
pathophysiological meaning of abrupt slowing
of the heart rate is not fully understood, but its
fundamental purpose in patients with IIB phobia can be speculated upon: Human beings have
a natural fear of blood and injury. In the normal
population exposure to blood or injury often results in disgust, discomfort, light-headedness or
even syncope. This kind of “emotional fainting”
is a reflex which is thought to be an evolutionary safety feature. According to Bracha et al.,
“the primary function of fear-induced faint­ing
may have been to non-verbally communicate to
equally preverbal adversaries that one was not an
immediate threat and could be safely ignored”
[7]. According to that hypothesis, syncope related to IIB phobia should occur rapidly as a way to
prevent injury.
The longer duration of the PR interval on the
baseline electrocardiogram is related to AVB during the neurocardiogenic reaction. That observation suggests that the vagal innervations of a cardiac
conduction system may be enhanced in vasovagal
patients with AVB during TT-induced syncope, or
that there is a subclinical intrinsic abnormality of
an atrioventricular node in these patients.
The significance of the type of neurocardiogenic reaction occurring during TT is usually
overlooked because it is presumed to have low reproducibility during spontaneous syncope [8, 9].
However, neurocardiogenic reactions are deemed
to have a stable electrocardiographic pattern during spontaneous syncope. It is puzzling that neurocardiogenic reactions of a given subject are similar except when induced by TT. The reason may be
a tendency to terminate TT at an earlier point than
the subject breaks the reflex in environmental circumstances by finding a suitable place to lie down.
In a previously published paper the authors
of the current study reported that the cardiodepressive type of neurocardiogenic reaction has the
highest reproducibility [8, 9]. This type of neurocardiogenic reaction is very common during carotid sinus massage, and it has been reported that
those patients had a similar type of the neurocardiogenic reaction during spontaneous syncopal
spells [10].
If the termination of TT occurs too early, the
vasodepressive type of neurocardiogenic reaction
predominates, similarly as in daily life circumstances an immediate assumption of a supine position, during the initial phase of vasovagal reflex
can terminate the reaction. This can lead to presyncope with tachycardia and without the heart
rate slowing and syncope [11, 12].
311
The differences observed between clinical and
electrocardiographic parameters within the groups
of patients presenting with and without AVB indicate the non-random nature of the groups’ differentiation. The presence of AVB during tilt testinduced neurocardiogenic reaction should alert
the physician performing the test to the possibility that the patient could experience such sudden
reflex reactions in everyday life due to emotional
factors.
The k-means cluster analysis that was performed to assess the homogeneity of the group of
patients with AVB showed two populations of different ages. In the younger subgroup there were
more women, IIB phobia reactions were more frequent and the mean PR interval was much shorter.
The duration of the slowing of the heart rate did
not differ between the two subgroups.
CART analysis permits the identification of
previously unrecognized patient subgroups and
is a useful method for dissecting complex clinical
situations and identifying heterogeneous patient
populations.
In the current study, the CART analysis basically separated the vasovagal patients into those
who experienced neurocardiogenic reaction in response to the sight of blood, instrumentation or
injection, and in those who did not do so. This
finding is in line with the theory that AVB during
neurocardiogenic reaction could be a mechanism
for enabling a fast and total loss of consciousness.
The presence of neurocardiogenic reactions in response to IIB in daily life circumstances predicts
the increased probability of AVB occurrence during TT-induced vasovagal syncope. In the group
with IIB phobia, female gender is the second factor related to the AVB occurrence: women are
more prone than men to have syncope in response
to IIB [7]. In the group without IIB phobia, the
branching of the CART analysis is caused by the
duration of the PR interval, the duration of the
slowing of the heart rate during the neurocardiogenic reaction and by gender.
The authors concluded that patients with
AVB during TT differ from those without AVB,
a sudden onset of a syncopal event, particularly in
women or in patients of either gender with instrumentation-injection-blood phobia, can indicate
AVB during vasovagal syncope. The population of
subjects with AVB during TT is not homogenous;
it consists of a younger subgroup with IIB phobia,
and an older subgroup with a concealed organic
AV node dysfunction.
312
J. Gajek et al.
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Address for correspondence:
Jacek Gajek
Department of Cardiology
Wroclaw Medical University
Borowska 213
50-556 Wrocław
Poland
Tel.: 48 605 433 321
E-mail: [email protected]
Conflict of interest: None declared
Received: 18.03.2011
Revised: 6.04.2011
Accepted: 2.06.2011