Download Clinical characteristics of patients with vasovagal reactions

Europace (2001) 3, 141–146
doi:10.1053/eupc.2001.0155, available online at http://www.idealibrary.com on
Clinical characteristics of patients with vasovagal
reactions presenting as unexplained syncope
L. A. Graham and R. A. Kenny
Cardiovascular Investigation Unit, Royal Victoria Infirmary, Newcastle upon Tyne, U.K.
Objective To describe the clinical characteristics of
vasovagal syncope (VVS) in patients presenting to a tertiary
referral centre with unexplained syncope, in whom the
diagnosis of VVS was confirmed by tilt table testing (HUT)
and in whom other causes of syncope excluded.
Design Prospective study of 62 consecutive patients with
more than two episodes of syncope in the past year.
Setting A regional tertiary referral centre for patients with
unexplained syncope.
Patients Sixty-two patients, mean age 5021 years, 39
female, were studied. Mean duration of symptoms was
5 years. Average frequency of attacks was one episode
per week.
Interventions Detailed semi-structured questionnaires
were completed regarding presenting symptoms.
Results In over one-third of patients, episodes occurred
suddenly, with no prodromal features. In those with
Background
Syncope is a term used to describe transient loss of
consciousness lasting for seconds to a few minutes,
resulting from temporary cessation of cerebral function.
Loss of postural tone with spontaneous and complete
recovery is typical. Usually there are no residual symptoms and no associated injuries. Syncope accounts for
6% of Accident & Emergency attendances and for up to
3% of hospital admissions[1]. Vasovagal syncope (VVS),
neurally mediated hypotension due to vasodilatation
Manuscript submitted 21 June 2000, and accepted after revision
28 January 2001.
Correspondence: Professor R. A. Kenny, Cardiovascular
Investigation Unit, Royal Victoria Infirmary, Newcastle upon
Tyne NE1 4LP, U.K. E-mail: [email protected]
1099–5129/01/020141+06 $35.00/0
prodrome, 71% had autonomic symptoms, but 27% had
palpitations or dyspnoea and 21% had chest pain.
Eleven percent of patients denied known provocative
features. In the remainder, the most common were prolonged standing (37%), hot weather (27%) and lack of food
(23%). One-fifth had symptoms sitting and 5% whilst
driving.
Seventy-five percent of patients suffered after effects, the
most common being severe fatigue. Over half sustained an
injury during syncope, and 13% sustained a fracture. Unwitnessed episodes occurred in 25%. Pallor was reported in
half the cases, sweating in 13% and myoclonus in 5%.
Conclusions Atypical presentations of VVS occur in
many patients referred to a tertiary referral centre.
Knowledge of the clinical characteristics of unexplained
syncope for which VVS is the attributable diagnosis should
assist in appropriate management of such patients.
(Europace 2001; 3: 141–146)
2001 The European Society of Cardiology
Key Words: Syncope, vasovagal syncope, tilt table testing.
and augmented vagal activity, is the most common cause
of syncope.
The diagnosis can often be made from the history: a
known provocative situation, pre-syncopal symptoms, a
witnessed ‘faint’ and no serious sequelae. Cases where
the cause is unclear, injury is sustained, episodes are
recurrent or other comorbidity is present make it more
difficult to attribute a diagnosis, and such patients are
referred for further assessment.
Tilt table testing (HUT) has been used for over 10
years to identify patients with hypotension and sometimes bradycardia, using reproduction of symptoms to
confirm a diagnosis of VVS[2]. The clinical characteristics of this group of patients with VVS confirmed as the
diagnosis following referral to a tertiary referral centre
has not been previously detailed. The objective of this
study was to clarify the clinical features of this group to
assist in early identification and appropriate referral of
such patients.
2001 The European Society of Cardiology
142
L. A. Graham and R. A. Kenny
Methods
A consecutive series of patients referred to a regional
syncope referral centre who had more than two episodes
of syncope in the previous year were prospectively
recruited. All patients had full history and examination
and investigations including 12-lead electrocardiograph,
supine and upright carotid sinus massage, 24-h ambulatory heart rate monitoring (Reynolds) and ambulatory
blood pressure (Spacelabs) revealed no attributable
cause for symptoms. Electro-encephalogram, echocardiogram, CT head scan and exercise testing were carried
out in selected cases if indicated. At the time of tilt table
testing, syncope remained unexplained. Those patients
who had reproduction of symptoms accompanied by
haemodynamic changes during head-up tilt (HUT) testing were invited to participate in further study to
elucidate the clinical characteristics of this group. Local
ethical approval was obtained and the patients gave
informed consent for further study.
Head-up tilt studies took place as day-cases between
14.00 and 16.00 h in a fasting state to avoid the postprandial hypotension effect. Avoidance of nicotine,
caffeine and alcohol was carried out for 24 h prior
to testing. All medications were continued as usual.
Continuous non-invasive monitoring of blood pressure
using the finger plethysmography method (OhMeda
Finapres) and surface ECG monitoring were applied
during all tilts.
Tilt test protocols
After lying supine for 10 min, unprovoked HUT at 70
was carried out for a maximum 40 min, or to development of symptoms[3]. Subjects who had a positive
response to unprovoked HUT, defined as development
of typical syncopal symptoms accompanied by hypotension and sometimes bradycardia, did not undergo
further testing with isoprenaline or glyceryl trinitrate
(GTN).
Isoprenaline HUT was carried out according to a
standard protocol[4], after intravenous cannulation.
Graded infusion of 0, 1, 3 and 5 g . min 1 was infused
with 5 min supine and 5 min in 70 tilt position with a
2-min rest supine between each increment in dose.
GTN HUT was carried out after 5 min lying supine.
GTN (800 g) was applied sublingually and subjects
were tilted to 70 for up to 25 min[5].
A positive test was defined as reproduction of
patient’s usual symptoms (syncope or profound presyncope), accompanied by hypotension (fall in systolic
blood pressure of greater than 50 mmHg from baseline
or to less than 70 mmHg), and sometimes bradycardia
(heart rate less than 60 bpm). These patients were
diagnosed as having VVS and asked to complete
questionnaires.
Questionnaire
Semi-structured questionnaires were completed on a
separate day to tilt table testing. Details of past medical
Europace, Vol. 3, April 2001
history, including cardiovascular disease, cerebrovascular disease, migraine and neurological disorders, were
recorded. A family history of syncope or pre-syncope, a
history of childhood fainting episodes, and medication
were noted. Circumstances in which the episodes
occurred (specific situations being derived from previous
qualitative interviews of syncopal patients and from
volunteered information) were detailed. The presence
and characteristics of prodrome were similarly explored.
Details of witness’ accounts of events were also noted.
Associated signs and symptoms after the event and
consequences such as hospital attendance or injury were
recorded. The questionnaire was piloted on a group of
15 patients prior to study commencement. During the
study, questionnaires were taken away by patients to be
completed following the initial HUT test. On return for
the next appointment, the doctor or nurse involved in
the study reviewed all answers with the patient for any
necessary clarification.
Results
From September 1996 to September 1997, 99 patients
referred to a tertiary referral centre underwent tilt table
testing in the absence of any other cause identified for
syncope. Seventy-four patients had a positive tilt table
test with reproduction of symptoms, confirming VVS as
the attributable cause. Twelve patients were unsuitable
(e.g. due to dementia) or unwilling to take part in further
study. Thus, 62 patients who had a positive tilt test in
the absence of another cause for syncope constituted
the study group. Mean age was 50 years (21 years)
and 39 (63%) were female. Half (n=31) of the patients
required drug provocation to provoke a positive tilt
response. Twenty-one of these patients had positive
GTN tilts and 10 had positive isoprenaline tilts at a
mean dose of 31 g . min 1. Mean time to positive
test for unprovoked HUT was 2110 min, GTN HUT
105 min and isoprenaline 279 min. Mean fall in
blood pressure from baseline was 5720 mmHg and
bradycardia occurred in 18 patients.
Twenty-five patients had negative tilt tests and syncope remained unexplained at the end of the study.
Mean age was 5217 years and 17 (68%) were female.
Clinical features of VVS
Median symptom duration was 5 years (range 3
months–30 years). Frequency of attacks ranged from
daily to twice a year, with the mean frequency being one
episode per week. Loss of consciousness always occurred
in 28 (45%) patients. Forty-eight percent had isolated
episodes of pre-syncope as well as syncope. Prodromal
features were absent and sudden loss of consciousness
with no warning occurred in 24 (39%) cases. Attacks
tended to follow a cluster pattern in 16 (26%). Seven
percent felt there was a seasonal variation, with attacks
Vasovagal reactions presenting as unexplained syncope
Table 1 Characteristics and comorbidity of patients with
vasovagal syncope
Feature
Table 2
143
Precipitants of vasovagal syncope
Precipitant
Number (n=62)
%
23
17
14
13
13
12
10
7
7
7
6
6
4
4
4
4
4
37
27
23
21
21
19
16
11
11
11
10
10
6·5
6·5
6·5
6·5
6·5
No of patients n=62 (%)
Age (years)
Female sex
Duration of symptoms
Frequency of episodes
Hypertension
Respiratory disease
Ischaemic heart disease
Cerebrovascular disease
Cardiovascular medications
5021
39
Mean 5 years
(range: 3 months–30 years)
Mean 1/week
(range: daily–2/year)
8 (12·9)
8 (12·9)
6 (9·7)
6 (9·7)
10 (16)
more frequent in either summer or winter in half the
cases. Eleven percent of patients noted more frequent
symptoms in the morning.
Comorbidity was present in 32 (53%) of patients and
is detailed in Table 1. Eight subjects had a history of
hypertension, six ischaemic heart disease, six cerebrovascular disease, six asthma, three chronic obstructive airways disease and one mild valvular heart disease (mild
mitral and tricuspid regurgitation). Childhood or teenage fainting was present in 7 (27%) cases. Three patients
had migraine and three had tinnitus. One suffered from
epilepsy and one had atrial fibrillation.
A family history of vasovagal syncope was present in
18 (29%) cases.
Medications
Cardio-active medications were being taken in 12
patients for control of ischaemic heart disease or hypertension. Calcium antagonists in six patients, betablockers in three, diuretics in two and digoxin in one.
Three patients were taking a combination of cardioactive medications. Ten percent of patients were taking a
nitrate medication, with nine of these using GTN spray.
Three patients were on the oral contraceptive pill and
one was on hormone-replacement therapy. No patients
were taking herbal remedies. Six patients were on nonsteroidal anti-inflammatory drugs (NSAIDS), six on
inhaled beta-agonists and five on vestibular sedatives.
Two were on antimigraine medication and one was on
anticonvulsant therapy.
Precipitants of VVS
Precipitating factors are detailed in Table 2. Seven
patients (11%) were unable to identify any specific
precipitants for their attacks. The most common precipitants were hot weather (37%), prolonged standing (27%)
and lack of food (23%). Twenty-one percent of patients
had attacks in response to emotional stimuli or head
movement. Nineteen percent experienced symptoms
Hot weather
Prolonged standing
Lack of food
Emotion
Head movement
Sitting
Early mornings
Venepuncture
Post-prandial
Cold weather
Alcohol
Medication
Illness
Hairdressers
Pregnancy
Saunas
Fear
while sitting and 5% while driving. Coughing, the sight
of blood, restaurants and pre-menstrual symptoms gave
rise to episodes in 5%. Dental surgery, funerals, minor
surgery, defaecation and micturition, weddings, horror
films, rock concerts and postpartum syncope occurred in
less than 2% of this population.
Prodromal features
Prodromal features were absent in 24 (39%). There were
no significant clinical differences between those patients
with and those without prodrome.
Where prodrome was present, the most common
features were light-headedness in 35 (92%) patients,
fatigue in 26 (68%), blurred vision in 26 (68%), sweating
in 25 (66%) and nausea in 23 (60%). Fourteen (37%)
had palpitations prior to syncope, and 14 (37%) had
shortness of breath. Headache occurred in 11 (29%) and
chest pain in one-quarter. Dizziness was uncommonly
reported (5%) compared with the more specific term
‘light-headedness’, which was the most common
prodrome (Table 3).
Morbidity of VVS
Symptoms persisted after syncope were experienced in
47 (76%) patients. The most common were fatigue in 29
(47%); light-headedness in 25 (45%); disorientation in 20
(32%); nausea in 17 (27%); confusion in 14 (22%) and
palpitations in 12 (19%). Ten (16%) reported excessive
warmth or sweating, and two (3·2%) were incontinent of
urine.
Fifty-three percent (n=33) reported significant injury
due to their syncopal episodes. Twenty-nine of these
patients attended Accident & Emergency departments
for treatment. Significant soft tissue injury was present
Europace, Vol. 3, April 2001
144
L. A. Graham and R. A. Kenny
Table 3
Prodromal features of vasovagal syncope
Symptom
Light-headedness
Fatigue
Blurred vision
Sweating
Nausea
Fading vision
Palpitations
Shortness of breath
Headache
Coldness
Chest pain
Tingling
Flushing
Abdominal pain
Dizziness
Apprehension/fear
Number (n=38)
%
35
26
26
25
23
16
14
14
11
11
8
7
7
2
2
2
92
68
68
66
60
42
37
37
29
29
21
18
18
5
5
5
in 15 and lacerations requiring suturing were present in
three. Three had head injury requiring an advice card
prior to discharge.
Eight (13%) patients had fractures; four were of the
wrist, and one each of the foot, ankle, elbow and ribs.
Witness accounts
No witness account was available in one-quarter of
cases. Pallor was seen in 30 (48%) patients, sweating in
eight (13%), weak or absent pulse was noted in two (3%)
and twitching or jerking in three (5%). A combination of
these features, which might suggest a diagnosis of VVS,
was not reported by witnesses. Seven subjects had pallor
and sweating, and one had weak pulse and pallor.
Comparison with patients with negative tilt
tests
Compared with those with a positive test, the 25 patients
whose syncope remained unexplained reported no significant differences in terms of frequency or duration of
episodes, comorbidity, the use of cardiovascular medications or precipitants of syncope. These patients were
less likely to feel unwell after syncope, although 32%
reported experiencing significant injury and 4% had
fractures. Sudden loss of consciousness with no prodrome occurred in four (16%) patients compared with 38
(62%) of the tilt positive group (P<0·001). Prodromal
features of light-headedness, fatigue and blurring of
vision were less frequently reported. Isolated episodes of
pre-syncope and clustering of attacks were also less
likely to occur.
Frequency of syncopal episodes
Patients with frequent episodes of syncope, defined as
more than one episode per month, were significantly
Europace, Vol. 3, April 2001
younger than those with occasional syncope (4521
years vs 6114 years, P=0·004). Two-thirds of each
group were female. Clustering of episodes occurred in
two (10%) infrequent fainters, compared with 14 (42%)
frequent fainters (P=0·01). There were no other significant differences in the clinical presentation of those
with frequent syncope, compared with those with more
occasional symptoms.
Discussion
Vasovagal reactions are the most common cause of
syncope. In patients with unexplained syncope, it has
been estimated that 36–57% have vasovagal syncope[6].
Prior to the introduction of tilt table testing in 1986[2],
the diagnosis of VVS depended on clinical description
alone.
Sir Thomas Lewis’ classic description of VVS following venesection in 1932 details dizziness, pallor, weak
slow pulse, retching and confusion followed by unconsciousness and profound hypotension[7]. Not all histories
are as clear cut, and a clinical diagnosis can be difficult
to reach in patients without classic prodromal symptoms
or an obvious provoking stimulus.
In 1961, Wayne described the features of syncope in
500 cases. In 298 patients, a vasovagal diagnosis was
attributed, predominantly due to a history of a specific
precipitant[8]. Cases were of all ages and males were
more commonly afflicted than females. Precipitants included emotional tension, fatigue, alcohol ingestion and
lack of sleep.
The advent of tilt table testing affords more accurate
diagnosis. This study is the first to quantify the clinical
characteristics of patients referred for tilt table testing
with recurrent VVS, who do not have any other
diagnosis to explain their symptoms.
The most striking feature is the absence of prodrome
in 39% of cases. This has been reported previously, and
has been termed ‘malignant VVS’[9]. Injuries are likely to
occur as the patient has very little warning of attacks
and injuries were frequent in this series. Absence of
classic prodromal symptoms may suggest other causes
for syncope. Clustering of episodes occurred in onequarter of patients, not necessarily in the summer
months. Childhood fainting recurring in later life has
been described and confirmed in this series[10]. Twentynine percent of patients had a family history of VVS.
Mathias et al. reported a family history in 24 of 47 (51%)
patients with definite VVS[11], with history of syncope in
a parent being the most common scenario. However, to
the authors’ knowledge, no genetic studies have been
conducted.
Hypertension or vascular disease was present in
half the patients. Treatment options and precipitant
medications are often curtailed for these patients.
No previous studies have detailed precipitating factors. Eleven percent of patients were unable to identify a
specific precipitant. Calkins et al. compared clinical
characteristics of patients with atrioventricular node
Vasovagal reactions presenting as unexplained syncope
disease, ventricular tachycardia and VVS as causes of
syncope confirmed by electrophysiological studies or
isoprenaline HUT[12]. In the vasovagal group (32
patients), 38% did not have a specific precipitant.
The most common precipitants noted in this study are
well recognized. However, symptoms are not necessarily
associated with upright posture and a small number of
patients reported symptoms whilst driving. Head movement was a common precipitant, despite the fact that
carotid sinus syndrome was excluded in all patients.
Situational syncopes — coughing, micturition and
defaecation — were uncommon and classic scenarios
such as restaurants, weddings and rock concerts were
not frequent precipitants. Symptoms whilst driving
occurred in 5% of cases, one of whom had had an
accident. Sheldon et al. reported that five of 209 VVS
patients with positive isoprenaline HUT had had symptoms whilst driving; four of these had had accidents[13].
Accurate diagnosis and counselling were felt to reduce
the risk. Current advice for driving in the U.K. is that
patients must be free of syncope for 6 months following
a diagnosis[14].
The classic prodromal features of nausea, sweating
and warmth were not the most common presentations.
Light-headedness and fatigue were more evident.
Potentially confusing features such as palpitations, chest
pain and shortness of breath occurred in a significant
number of patients. These findings are similar to those
reported by Calkins et al.[12]. Dizziness was a relatively
uncommon feature, with a specific feeling of lightheadedness being more commonly reported. Although
dizziness and syncope co-exist in up to 70% of syncopal
patients, a rotatory dizziness (giddiness) is more likely to
be associated with a psychiatric diagnosis than with
VVS[15].
How patients feel after an episode may be one of the
strongest indicators of VVS. Three-quarters of patients
suffered after effects of their attacks. Profound fatigue
was the most common after effect, and light-headedness
was also prominent feature. One-fifth of patients
reported palpitations or confusion. No studies have
detailed, specifically, injuries due to VVS. Half of
patients with carotid sinus syndrome experience injury
and 25% sustain fractures due to their syncope[16]. Injury
rates are lower in VVS but significant injuries, particularly fractures, did occur in 13% of this series. The
difference may be related to age or due to the lower
prevalence of prodrome in carotid sinus syndrome.
Witness accounts were only available in three-quarters
of cases. Pallor was the most common feature. No
classic reports of pallor, sweating and slow pulse were
given. Twitching or jerking and also the presence of
incontinence can lead to misdiagnosis as epilepsy resulting in inappropriate use of anti-epileptic medication[17].
Conclusions
Features which characterize classical vasovagal syncope
are not present in many patients referred to a tertiary
145
referral centre who have VVS as an attributable cause of
symptoms. Patients represent a broad age distribution
and generally experience frequent symptoms. Known
provocative factors for situational syncope occur in half
of these patients. Over one-third will not experience
prodrome, but in those who do, chest pain and palpitations can occur. Episodes can occur whilst seated and
whilst driving. Light-headedness and fatigue are common after effects. Comorbidity is often present and
medications are commonly implicated. Witness accounts
if available are often unhelpful. A positive family
history, clustering of episodes and childhood fainting
are helpful historical findings. Significant morbidity
occurred in more than half of the patients in this series
knowledge of the clinical characteristics of unexplained
syncope for which VVS is the attributable diagnosis
should assist in appropriate referral of such patients for
tilt table testing.
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