A new test for diagnosing vasovagal syncope: Standing after treadmill test with sublingual nitrate administration
June
A new test for diagnosing vasovagal syncope: Standing after treadmill test with sublingual nitrate administration
Tae-Hoon Kim 0 1 2
Ho-Jun Jang 0 2
Sihun Kim 2
Sung Yun Cho 2
Kyung Sun Song 2
Christopher Pickett 1 2
Heiko J. Schmitt 1 2
Juyong Lee 1 2
0 Division of Cardiology, Sejong General Hospital , Bucheon, Gyeonggi-Do , Republic of Korea, 3 Department of Neurosurgery, New Korea Hospital , Gimpo, Gyeonggi-Do , Republic of Korea
1 University of Connecticut Health Science Center , Farmington, Connecticut , United States of America
2 Editor: Yoshihiro Fukumoto, Kurume University School of Medicine , JAPAN
Increased adrenergic tone might be an additional trigger of orthostatic stress of vasovagal syncope (VVS). Exercise before standing might provide increased sensitivity compared to standing using a sublingual nitroglycerines protocol during tilt table testing. The aim of this study was to evaluate the diagnostic value of treadmill testing before standing with nitroglycerin administration.
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Data Availability Statement: All relevant data are
within the paper and its Supporting Information
file.
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
Methods and results
A total of 36 patients with syncope or presyncope were enrolled for the test. VVS was
confirmed in 29 patients according to the Calgary Score ( -2), including 20 patients who were
likely to have typical (classical) VVS. All 36 subjects were subjected to a novel provocation
test consisting of treadmill test using the Bruce protocol followed by standing with
administration of 300 μg sublingual nitroglycerin. Consequently, syncope or presyncope occurred in
22 patients of the 36 patients. The sensitivity and a specificity of the test for Calgary score
based VVS was 82.7% and 85.75%, respectively. Reproducibility rate for typical VVS was
90% (18 of 20). In all symptomatic patients, systolic blood pressure dropped to < 90 mmHg
and symptom occurred a mean of 6.7 ± 2.3 minutes after the nitroglycerine administration.
No patient required anticholinergics injection to restore vital signs.
Conclusions
Treadmill test with administration of sublingual nitroglycerines might be safely used to reproduce syncope in patients with VVS. More clinical experience and confirmation are needed to validate this protocol.
Introduction
Vasovagal syncope (VVS) is the most common type of reflex syncope. It is usually mediated by
orthostatic posture. However, not all patients have syncopal episodes while standing. Increased
adrenergic tone such as emotional stress or pain may trigger and contribute to VVS. Although
VVS is frequently associated with more complex situations with various stressors and
circumstances [
1
], increased adrenergic tone is thought to be the common trigger toward standing in
general. Adrenergic surge after prolonged standing is believed to be a key initiating factor of
tilt test using isoproterenol [
2
]. Currently, tilt test using intravenous isoproterenol or
sublingual nitroglycerin is widely used for the patients to confirm VVS. However, the reproducibility
rates have stayed at approximately 40~50% for VVS patients in each protocol [
3
]. We
hypothesized that increased adrenergic tone by exercise could be an additional trigger toward the
venous pooling stress. If so, the treadmill exercise test (TMT) could be employed to provoke
syncope or presyncope in patients suspected to have VVS. The aim of this study was to
evaluate the diagnostic value of standing after TMT with sublingual nitrate administration for VVS.
Materials and methods
Study population
From August 2015 to July 2016, patients with syncope or presyncope of unknown origin pre
sented to our hospital. Careful history was taken either by the Department of Cardiology or
Neurosurgery. Second, physical examination including routine laboratory tests, orthostatic
blood pressure (BP) measurements during 3 minutes after standing, electrocardiogram (ECG),
and echocardiography were performed for all patients in the Department of Cardiology.
Neurologic examination with or without imaging test including brain magnetic resonance imaging
and computed tomography were performed in the Department of Neurosurgery. Finally, all
subjects without orthostatic hypotension (BP decrease 20/10 mmHg), organic heart disease,
or neurological abnormality were enrolled.
Study definitions and diagnosis of VVS
Syncope was defined as abrupt loss of consciousness with inability to maintain postural tone
but with spontaneous recovery. Presyncope was defined as presence of symptoms of imminent
syncope with difficulty in maintaining postural tone [
4
]. A positive test result of sublingual
nitroglycerin TMT was defined as reproducing the spontaneous syncope or impairment of
sustain of standing due to symptoms of presyncope regardless of their vital signs. Seven
diagnostic questions about medical histor (...truncated)