korean j intern med 2012;27:60-65
pISSN 1226-3303 eISSN 2005-6648
Positive Result in the Early Passive Phase of the Tilt-Table
Test: A Predictor of Neurocardiogenic Syncope in Young
Jae-Sun Uhm1, Ho-Joong Youn1, Woo-Baek Chung1, Yun-Seok Choi1, Chul-Soo Park1, Yong-Seog Oh1, Wook-Sung
Chung1, Kyung-Il Park2, and Tae-Suk Kim3
1Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul; 2Division
of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul; 3Department of Internal
Medicine, Armed Forces Capital Hospital, Seongnam, Korea
Background/Aims: This study elucidated the prognostic factors for neurocardiogenic syncope in males in their late teens
and early twenties.
Methods: Tilt-table testing (TTT) was performed on 665 males (age range, 17 to 27 years) following the Italian protocol.
The subjects were tilted head-up at a 70° angle on a table for 30 minutes during the passive phase. If the passive phase
was negative, the subjects were given sublingual nitroglycerin and tilted to the same angle for 20 minutes during the drug-
provocation phase. The subjects with positive results were followed without medication. We analyzed factors related to the
recurrence rate of syncope.
Results: Of 305 subjects (45.8%) with positive results, 223 (age range, 18 to 26 years) were followed for 12 months.
The frequency of previous syncopal episodes ≥ 4 (p = 0.001) and a positive result during the passive phase (p = 0.022)
were significantly related to a high recurrence rate. A positive result during the early passive phase (≤ 12 minutes) was
significantly related to a higher recurrence rate than was that during the late passive phase (> 12 minutes; p = 0.011).
Conclusions: A positive result during the early passive phase of TTT and frequent previous syncopal episodes were
prognostic factors for neurocardiogenic syncope in men in their late teens and early twenties.
Keywords: Syncope, vasovagal; Prognosis; Tilt-table test
Neurocardiogenic syncope is the most common cause of
syncope in patients without underlying disease . Neu-
rocardiogenic syncope has a peak incidence in subjects
in their late teens and early twenties . Tilt-table testing
(TTT) is used widely to diagnose neurocardiogenic syn-
cope. The positive rate of TTT with or without a history of
syncope ranges from 23.8 to 74% [3-6]. Many research-
ers have studied treatments of neurocardiogenic syncope
including salt intake , physical maneuvers [8,9], beta-
blockers [10,11], midodrine , fludrocortisones , par-
oxetine , and cardiac pacing ; however, the results
are conflicting. In general, the prognosis of patients with
Copyright © 2012 The Korean Association of Internal Medicine
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-
commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received : march 9, 2011
Revised : June 17, 2011
Accepted : October 5, 2011
Correspondence to Ho-Joong Youn, M.D.
Cardiovascular Center, Seoul St. mary’s Hospital, 222 Banpo-daero, Seocho-gu, Seoul 137-701, Korea
Tel: 82-2-2258-1134, Fax: 82-2-2258-1506, E-mail: firstname.lastname@example.org
Uhm JS, et al. Prognosis for neurocardiogenic syncope 61
neurocardiogenic syncope is benign, although some pa-
tients experience not only recurrent syncopal episodes but
also serious head injuries despite treatment. Therefore,
the identification of high-risk patients is important for
treatment and follow-up. The frequency of previous syn-
copal episodes has been reported to be the most powerful
predictor of recurrent neurocardiogenic syncope [16-21].
No other prognostic factors have been confirmed for males
in their late teens and early twenties. Therefore, this study
sought to identify prognostic factors for neurocardiogenic
syncope in males in their late teens and early twenties.
Consecutive males with unexplained syncope seen
between September 2006 and September 2008 were
included. Subjects with underlying disease or abnormal
electrocardiograms (ECGs) and those taking any medica-
tions were excluded. Abnormal ECGs included rhythms
other than sinus rhythm, right- or left-axis deviation, left-
or right-ventricular hypertrophy, Mobitz type 2 second-
degree atrioventricular block, complete atrioventricular
block, left bundle-branch block, and pathological Q-wave
and abnormal ST-segment or T-wave changes.
TTT was performed according to the Italian protocol
[22,23]. The subjects fasted for at least 3 hours before the
test. The subjects were monitored throughout testing with
3-lead electrocardiography and automated blood pressure
cuff measurements every 2 minutes. The TTT consisted
of passive and drug-provocation phases. After a 5-minute
rest in the supine position, the subjects were tilted head-
up to a 70° angle on the table for 30 minutes during the
passive phase. If the passive phase was negative, the sub-
jects were given sublingual nitroglycerin (0.4 mg) and
tilted to the same angle for another 20 minutes during the
drug-provocation phase. The endpoint of the TTT was the
induction of syncope with significant hypotension. Posi-
tive results were classified into the following three types
[22,24]: type 1 (mixed) was defined as hypotension and
heart rate 40-60/minutes; type 2 (cardioinhibitory) was
defined as heart rate < 40/minutes or asystole for ≥ 3 sec-
onds; and type 3 (vasodepressor) was defined as pure hy-
potension without bradycardia. Hypotension was defined
as decreased blood pressure causing syncope or signs of
poor tissue perfusion. The subjects with positive results
were educated on the prevention of syncope, including the
avoidance of predisposing factors, lying down at the onset
of prodromal symptoms, fluid or salt intake, and physical
maneuvers. No medications were prescribed for subjects
with positive results. The subjects were followed in the
outpatient clinic or by telephone on a regular basis for 12
months. All subjects provided informed consent.
We analyzed the frequency of previous syncope, the TTT
phase that gave a positive result, the TTT duration until a
positive result, the types of neurocardiogenic syncope, and
the recurrence rate of syncope during the follow-up period.
The results are expressed as the mean ± SD or median (in-
terquartile range, IQR) for data that were not distributed
normally. The Mann-Whitney U test and Kruskal-Wallis
test were used for statistical analysis of data that were not
distributed normally. Univariate and multivariate logistic
regression analyses were used to identify variables associ-
ated with the recurrence of syncope during the follow-up
period. A p value < 0.05 was considered significant. The
data were analyzed with the SPSS version 12.0 (SPSS Inc.,
Chicago, IL, USA).
Of the 665 male subjects (mean age, 22.0 years; range,
17 to 27) who underwent testing, 305 (45.8%) had positive
results on TTT. Of the subjects with positive results, 82
were excluded because of abnormal ECGs or loss to follow-
Tilt-table test (n = 665)
Positive (n = 305)
Negative (n = 360)
Exclusion (n = 82)
Drug provocation phase (n = 178 / 223) Passive phase (n = 45 / 223)
Figure 1. Flow diagram and number of subjects. Eighty-two
patients were excluded because they were lost to follow-up or be-
cause they took medicine.
62 The Korean Journal of Internal medicine Vol. 27, No. 1, march 2012
up (Fig. 1). We followed 223 subjects (mean age, 21.1 years;
range, 18 to 26) for 12 months. The frequency of previous
syncopal episodes was 3.4 ± 5.0 (Table 1).
Tilt-table test and follow-up results
There were 45 (20.2%) subjects with positive results
during the passive phase and 178 (79.8%) during the drug-
provocation phase (Fig. 1). There were 146 (65.5%), 39
(17.5%), and 38 (17.0%) type 1 to 3 subjects, respectively.
Syncope recurred in 67 (30.0%) subjects. The frequency
of recurrence of syncopal episodes during the follow-up
period was 1.3 ± 2.4. No recurrences occurred in 95 of 116
subjects (81.9%) with one previous syncopal episode, 36 of
54 subjects (66.7%) with two or three syncopal episodes,
and 25 of 53 subjects (47.2%) with four or more syncopal
Factors related to the recurrence of syncope
The subjects with four or more previous syncopal epi-
sodes in their lifetime had significantly more recurrences
of syncopal episodes than did those with fewer than four (1,
2-3, and ≥ 4; 0 [IQR, 0 to 0.5], 0 [IQR, 0 to 2], and 3 [IQR,
0 to 9.5], respectively; p = 0.001) (Fig. 2). The subjects with
positive results during the passive phase had significantly
more recurrences of syncope than did those with positive
results only during the drug-provocation phase (1 [IQR, 0
to 4] and 0 [IQR, 0 to 1], respectively; p = 0.022) (Fig. 3).
The subjects (n = 7 of 45) with positive results during the
early passive phase (≤ 12 minutes) had significantly more
recurrences of syncopal episodes than did subjects (n = 38
of 45) with positive results during the late passive phase
(> 12 minutes) (4 [IQR, 3 to 7] and 0 [IQR, 0 to 4], respec-
tively; p = 0.011) (Fig. 3). However, there were no signifi-
cant differences between the subjects with positive results
during the early (≤ 10 minutes, n = 146 of 178) and late
(> 10 minutes, n = 32 of 178) drug-provocation phases (0
[IQR, 0 to 2] and 0 [IQR, 0 to 0.5], respectively; p = 0.614)
or among the types of neurocardiogenic syncope (types
1 to 3; 0 [IQR, 0 to 1], 0 [IQR, 0 to 3], and 0 [IQR, 0 to 3],
respectively; p = 0.435) and the recurrence of syncope.
Frequent previous syncopal episodes (≥ 4; p = 0.001) and
positive results during the passive phase of TTT (p = 0.001)
were significantly associated with the recurrence of syn-
cope (Table 2).
This prospective, observational study elucidated prog-
nostic factors for neurocardiogenic syncope in males in
their late teens and early twenties in whom the incidence
of neurocardiogenic syncope is high . We found that
most subjects (81.9%) with one previous syncopal episode
Frequency of previous syncope
0 (0, 0.5)
2, 3 4-
0 (0, 2)
3 (0, 9.5)
p = 0.001
Figure 2. Recurrence of syncope according to the frequency of
previous syncopal episodes. The results are expressed as the me-
dian (interquartile range).
Table 1. Clinical characteristics of the subjects
Total no. of subjects 223
Age, yr 21.1 ± 1.6
male gender 223 (100)
Frequency of previous syncope, times3.4 ± 5.0
No. of subjects with 1 episode 116 (52.0)
No. of subjects wwith 2-3 episodes 54 (24.2)
No. of subjects with ≥ 4 episodes
Interval between the last episode
and tilt-table testing, day
60.6 ± 92.2
Values are presented as the mean ± SD or number (%).
Uhm JS, et al. Prognosis for neurocardiogenic syncope 63
had no recurrence and that frequent previous syncopal
episodes in their lifetime (≥ 4), a positive result during the
passive phase of TTT, and positive results during the early
passive phase (≤ 12 minutes) were significantly related to
the recurrence rate of syncope. Therefore, a positive result
during the early passive phase of TTT and frequent pre-
vious syncopal episodes might be prognostic factors for
neurocardiogenic syncope in males in their late teens and
In previous studies, the frequency of syncope before
TTT was the most powerful predictor for recurrent synco-
pe [16-20]. Female gender, a history of bronchial asthma,
and the number of previous syncopal episodes may predict
recurrences of neurocardiogenic syncope . However,
the TTT phase or period associated with positive results as
prognostic factors have not been studied in males in their
late teens and early twenties.
Neurocardiogenic syncope occurs frequently during
prolonged motionless standing, and the passive phase is
similar to this situation. The drug-provocation phase is
performed on subjects who can tolerate the passive phase.
Such subjects were better able to tolerate prolonged mo-
tionless standing. Therefore, subjects with a positive result
during the passive phase would tend toward a high recur-
rence rate of syncope. Furthermore, subjects with a posi-
tive result during the early passive phase could be more
1 (0, 4)
0 (0, 1)
p = 0.011
4 (3, 7)
0 (0, 1)
p = 0.022
Figure 3. Recurrence of syncope according to the phase with positive tilt-table testing results. (A) Comparison of subjects with positive
results during the passive and drug-provocation phases. (B) Comparison of subjects with positive results during the early and late pas-
sive phases. The results are expressed as the median (interquartile range).
Table 2. Univariate and multivariate logistic regression analyses to identify the variables that influence the recur-
rence of syncope
p valuep valueOR95% CI
Frequent previous syncopal episodes (≥ 4)0.0010.0017.857 2.938 - 21.010
Positive result during the passive phase of TTT0.0020.001 5.504 2.390 - 12.676
Types of neurocardiogenic syncope 0.435---
OR, odds ratio; CI, confidence interval; TTT, tilt-table testing.
64 The Korean Journal of Internal medicine Vol. 27, No. 1, march 2012
susceptible to a shorter duration of motionless standing.
The classification of neurocardiogenic syncope is based
on the results of TTT [22,24]. The mechanisms of each
type and the relationship between the type and prognosis
are debatable .
For patients suspected of neurocardiogenic syncope, it
is important to obtain a medical history and to perform
TTT. Patients with positive results during the early passive
phase of TTT and with more frequent episodes of previous
syncope need to be followed closely and treated optimally.
The follow-up period of our subjects was relatively short;
therefore, future prospective studies are needed to ascer-
tain the recurrence of syncope in more subjects for longer
periods of time at various centers. There are different TTT
protocols (e.g., the Westminster protocol using isoproter-
enol for the drug-provocation phase). The Italian protocol
with nitroglycerin is comparable to the Westminster pro-
tocol with isoproterenol [22,23].
A positive result during the early passive phase of TTT
and frequent previous syncopal episodes are significant
prognostic factors for neurocardiogenic syncope in males
in their late teens and early twenties.
Conflict of interest
No potential conflict of interest relevant to this article
1. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prog-
nosis of syncope. N Engl J Med 2002;347:878-885.
2. Colman N, Nahm K, Ganzeboom KS, et al. Epidemiology of re-
flex syncope. Clin Auton Res 2004;14 Suppl 1:9-17.
3. Youn HJ, Chung WS, Baek SH, et al. The usefulness of head-
up tilt test in the diagnosis of syncope of unknown origin and
clinical characteristics of the patients with vasovagal syncope.
Korean J Med 1994;47:186-194.
4. Shinohara M, Kobayashi Y, Obara C, et al. Neurally mediated
syncope and arrhythmias: a study of syncopal patients using
the head-up tilt test. Jpn Circ J 1999;63:339-342.
5. Jeong JO, Kim JS, Kim JK, et al. Head-up tilt test in subjects
with no history of syncope or presyncope. Korean Circ J
6. Turk U, Alioglu E, Kirilmaz B, et al. Prediction of head-
up tilt test result: is it possible? Pacing Clin Electrophysiol
7. El-Sayed H, Hainsworth R. Salt supplement increases plasma
volume and orthostatic tolerance in patients with unexplained
syncope. Heart 1996;75:134-140.
8. Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling
W. Management of vasovagal syncope: controlling or abort-
ing faints by leg crossing and muscle tensing. Circulation
9. Kim KH, Cho JG, Lee KO, et al. Usefulness of physical maneu-
vers for prevention of vasovagal syncope. Circ J 2005;69:1084-
10. Sheldon R, Connolly S, Rose S, et al. Prevention of Syncope
Trial (POST): a randomized, placebo-controlled study of
metoprolol in the prevention of vasovagal syncope. Circulation
11. Nakagawa H, Kobayashi Y, Kikushima S, et al. Long-term ef-
fects of pharmacological therapy for vasovagal syncope on the
basis of reproducibility during head-up tilt testing. Jpn Circ J
12. Kaufmann H, Saadia D, Voustianiouk A. Midodrine in neurally
mediated syncope: a double-blind, randomized, crossover
study. Ann Neurol 2002;52:342-345.
13. Scott WA, Pongiglione G, Bromberg BI, et al. Randomized
comparison of atenolol and fludrocortisone acetate in the treat-
ment of pediatric neurally mediated syncope. Am J Cardiol
14. Di Girolamo E, Di Iorio C, Sabatini P, Leonzio L, Barbone C,
Barsotti A. Effects of paroxetine hydrochloride, a selective se-
rotonin reuptake inhibitor, on refractory vasovagal syncope: a
randomized, double-blind, placebo-controlled study. J Am Coll
15. Connolly SJ, Sheldon R, Thorpe KE, et al. Pacemaker therapy
for prevention of syncope in patients with recurrent severe va-
sovagal syncope: Second Vasovagal Pacemaker Study (VPS II):
a randomized trial. JAMA 2003;289:2224-2229.
16. Sheldon R, Rose S, Flanagan P, Koshman ML, Killam S. Risk
factors for syncope recurrence after a positive tilt-table test in
patients with syncope. Circulation 1996;93:973-981.
17. Natale A, Geiger MJ, Maglio C, et al. Recurrence of neurocar-
diogenic syncope without pharmacologic interventions. Am J
18. Grimm W, Degenhardt M, Hoffman J, Menz V, Wirths A,
Maisch B. Syncope recurrence can better be predicted by his-
tory than by head-up tilt testing in untreated patients with sus-
pected neurally mediated syncope. Eur Heart J 1997;18:1465-
19. Kouakam C, Vaksmann G, Pachy E, Lacroix D, Rey C, Kacet S.