- Email: [email protected]
Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study
JACC: CLINICAL ELECTROPHYSIOLOGY
VOL.
-, NO. -, 2019
ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study Jayaprakash Shenthar, MD, DM,a,b Mukund Aravind Prabhu, MD, DM,a,b Bharatraj Banavalikar, MD, DM,a,b David G. Benditt, MD,a,b Deepak Padmanabhan, MD, DMa,b
ABSTRACT OBJECTIVES This study sought to determine the cause of recurrent syncope and clinical outcomes by using the head up tilt test (HUTT) and an insertable loop recorder (ILR) in patients with structural heart disease (SHD) and negative electrophysiology study (EPS) results. BACKGROUND Patients with syncope and SHD with negative EPS findings have a low risk of sudden cardiac arrest. Nevertheless, the cause of recurrent syncope and the outcomes in these patients are not well characterized. METHODS AND RESULTS This prospective study evaluated syncope patients with SHD and negative EPS results by using HUTT (with sublingual nitroglycerine [NTG] provocation as needed) and ILR. A total of 41 SHD patients (27 patients [66%] had coronary arterial disease, and 14 patients [34.15%] had dilated cardiomyopathy with mean EF of 42% 4.8% [range 30% to 49%]) were included. HUTT findings were positive in 25 patients (61%) in group A and negative in 16 patients (39%) in group B. An ILR was implanted in 21 of 25 group A patients (84%) and in 12 of 16 group B patients (75%), and they were followed for 15 8 months. During follow-up, 17 of 21 patients (81%) in group A and 5 of 12 patients (41.7%) in group B had ILR evidence consistent with reflex syncope. One group B patient had documented atrioventricular block and underwent pacemaker implantation. There were no malignant ventricular arrhythmias or deaths on follow-up. CONCLUSIONS Reflex syncope is the most common cause of syncope and accounts for approximately 60% of cases in patients with SHD, negative EPS results, left ventricular systolic dysfunction with left ventricular EF >30%, and not in heart failure. (J Am Coll Cardiol EP 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.
S
yncope/collapse is a common clinical condition
syncope per se does not necessarily herald an adverse
and is among the most frequent diagnoses
prognosis if there is no documented ventricular
leading to emergency department visits and
arrhythmia (5). In fact, it is estimated that among SHD
hospital admissions (1–3). Furthermore, in patients
patients with syncope, approximately one-third,
who had syncope in the setting of a structurally
including those with inducible arrhythmia episodes,
normal heart, a vasovagal reflex mechanism is the
may have reflex syncope (4); however, substantial
most common diagnosis (4,5).
uncertainty remains.
As a rule, mortality risk is low in reflex syncope
This study used an insertable loop recorder (ILR) to
patients, especially those without structural heart
determine the cause of recurrent syncope and assess
disease (SHD). Their major concerns are risk of injury
subsequent clinical outcomes in syncope patients
and impact on quality of life (6). In patients with SHD,
with SHD, no previously documented ventricular
From the aElectrophysiology Unit, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, Karnataka, India; and the bUniversity of Minnesota Medical School, Minneapolis, Minnesota. Dr. Benditt is supported in part by a grant from the Dr. Earl E. Bakken Family for Heart-Brain research; and is a consultant for and holds equity in Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received September 13, 2018; revised manuscript received January 29, 2019, accepted January 31, 2019.
ISSN 2405-500X/$36.00
https://doi.org/10.1016/j.jacep.2019.01.021
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ABBREVIATIONS
arrhythmia episodes, negative electrophysi-
block documented either on ECG or 24-h Holter and
AND ACRONYMS
ology study (EPS) findings, and a positive
patients with implanted devices such as pacemakers,
head up tilt test (HUTT) score.
implantable cardioverter-defibrillators, and cardiac
DCM = dilated cardiomyopathy EF = ejection fraction
resynchronization therapy devices, or if the patient
METHODS
did not give consent for the study. Patients with
EPS = electrophysiological
bundle branch block or bifascicular or trifascicular
study
HUTT = head-up tilt test ILR = insertable loop recorder
The present study was undertaken prospec-
block with a prolonged His to ventricle interval >70
tively in SHD patients with a history of
ms, abnormal sinus node function (i.e., corrected
recurrent syncope, evaluated at the syncope
sinus node recovery time >550 ms) on EPS were
LV = left ventricle
clinic of a tertiary care cardiac center in south
excluded. Patients treated with nitrates were also
NTG = nitroglycerine
India.
excluded because nitrate tolerance potentially affects
SHD = structural heart disease
approved the study, and all subjects con-
The
institutional
review
board
sented to the study.
the response to NTG provocation during HUTT. HUTT INTERPRETATION. The modified Vasovagal
INCLUSION CRITERIA. Study subjects consisted of
Syncope International Study (VASIS) classification
consecutive patients with a history of syncope, with
was used to classify the syncopal events during the
moderate left ventricular (LV) dysfunction due to
HUTT (8). Briefly, the responses associated with a
coronary arterial disease or DCM, no documented
positive HUTT were:
spontaneous ventricular tachyarrhythmia episodes on 24-h Holter recording, and negative EPS findings. All study patients underwent a thorough clinical history examination, either from the patient or from eyewitnesses if present, or both if possible. A compre-
Type 1 (mixed): heart rate drops at the time of syncope with the ventricular rate not <40 beats/min or is <40 beats/min for <10 s with or without asystole of <3 s.
hensive physical examination included postural blood
Type 2A: cardio-inhibitory without asystole; heart
pressure recordings. Cardiovascular system assessment
rate falls to a ventricular rate <40 beats/min for
also included 12-lead electrocardiography (ECG) and an
>10 s, but asystole of >3 s does not occur.
echocardiogram (i.e., chamber dimensions, valvular
Type 2B: cardio-inhibitory with asystole; asystole occurs >3 s, and heart rate fall coincides with or
function, and LV ejection fraction [LVEF]). A staff electrophysiologist evaluated the 12-lead
precedes blood pressure fall.
ECG and the 24-h Holter recording obtained from all
Type 3: vasodepressor; heart rate does not drop
study subjects. Coronary angiography and, when
more than 10% from its peak, but at the time of
necessary, cardiac magnetic resonance, were used to
syncope blood pressure falls precipitously.
evaluate the presence and severity of coronary arterial disease, DCM, or other SHDs. Inducible ischemia was excluded in patients with ischemic heart disease by treadmill test, dobutamine stress test, or stress thallium scan. EPSs were undertaken in all patients, consisting of assessment of sinus node function and atrioventricular (AV) conduction during the EPS. Programmed stimulation was performed at 2 cycle lengths (600 and 450 ms), with up to 3 extra stimuli from the right ventricular apex and right ventricular outflow tract to assess for inducibility of tachyarrhythmia episodes at baseline and with an infusion of isoprenaline at 1 to 4 mg/min to achieve a heart rate of 110 to 120 beats/min. Patients with negative EPS
findings
underwent HUTT, using nitroglycerin (NTG) provocation if needed (i.e., the Italian protocol) (7).
CLASSIFICATION OF ARRHYTHMIC EVENTS DURING HUTT. Development of new arrhythmia episodes that
were not present during the 30-min observation and baseline tilt were documented. An arrhythmia event was defined as tachyarrhythmia if the heart rate was >100 beats/min after excluding sinus tachycardia. The criterion for bradyarrhythmia was sinus rate of <40 beats/min, development of junctional rhythm, pause >3 s, or any degree of AV block. The criterion for premature beats was a newly developed atrial, junctional, or ventricular ectopic heart beats. A new onset arrhythmia episode such as atrial fibrillation, atrial tachycardia, ventricular tachycardia, or ventricular fibrillation that occurred during the test was considered a significant arrhythmic event. IMPLANTATION
OF
AN
INSERTABLE
LOOP
EXCLUSION CRITERIA. Exclusion criteria included
RECORDER. Implantation of an ILR was offered to all
documented
tachyar-
patients with negative EPS findings with or without a
rhythmia episodes, inducible ischemia, LVEF <30%,
positive HUTT result. In those who agreed to the
presence
implantation, a Reveal XT insertable cardiac monitor
of
or
inducible
heart
failure,
ventricular significant
bradyar-
rhythmias such as sinus node dysfunction, or AV
(Medtronic
Inc.,
Minneapolis,
Minnesota)
was
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F I G U R E 1 ILR Recording Showing Type IA Response
Insertable loop recording from a 46-year-old male showing typical reflex syncope with a type 1A response. Note the typical sinus tachycardia at the beginning, following which is sinus bradycardia and then sinus arrest during the episode of syncope.
implanted subcutaneously in the left parasternal
Type 3: no or slight rhythm variation.
area. The ILR was programmed to save up to 3 manual
Type 4: tachycardia. Increase in heart rate >30% or
activations of 7.5 min. Automatic activations were
>120 beats/min.
programmed to a) rapid ventricular tachycardia (R-R interval: 260 ms in at least 30 of 40 consecutive beats); b) ventricular tachycardia (R-R interval: 261 to 340 ms in 16 consecutive beats); c) a pause of >3 s; or d) bradycardia (heart rate: 30 beats/min in 4 consecutive beats). ILR recordings were retrieved as soon as was feasible in case of syncope and assessed for any ventricular or atrial tachyarrhythmia, and the heart rate response during the episode. The International Study on Syncope of Uncertain Etiology (ISSUE) classification was used to document ECG syncope on ILR (9). Briefly, the classifications were as follows:
FOLLOW-UP. After patients received ILR implanta-
tion, they were followed in the outpatient clinic every 3 months until a diagnosis was reached or until the end of service of the device. Once the device reached its end of service, it was explanted with no further replacement. and patients were followed in the outpatient clinic. In those cases in which the patient refused ILR implantation, they were followed in the outpatient clinic. Endpoints were either syncope recurrence or mortality. STATISTICAL ANALYSIS. Data are presented as mean
Type 1: asystole with R-R pause >3 s (type 1A sinus
SD. Patients’ data were compared using Fisher’s
arrest, type 1B sinus bradycardia plus AV block,
exact test. Continuous variables were compared using
type 1C AV block).
Student t-test in the case of normal distribution
Type 2: bradycardia with decrease in heart rate
of values and the nonparametric Mann-Whitney
>30% (type 2A) or <40 beats/min for >10 s
U test in the case of an asymmetric distribution. A
(type 2B);
p value < 0.05 was considered significant.
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F I G U R E 2 Insertable Loop Recording From a Patient With Issue Type 1c Response
Note that there is no increase in atrial rate prior to the onset of sudden AV block, resulting in ventricular asystole with regular P waves and no QRS. AV ¼ atrioventricular; ISSUE ¼ International Study on Syncope of Uncertain Etiology.
RESULTS
common response was the modified VASIS type III noted in 13 patients (52%), type I in 6 patients (24%),
From January 2010 to June 2015, 70 patients who had
type 2B in 5 patients (20%), and type 2A in 1 patient
syncope with SHDs were evaluated. Seven patients
(4%). There was a good correlation between the
were excluded from the study because they had
clinical symptoms and HUTT-induced symptoms in
documented episodes of symptomatic ventricular
these patients.
arrhythmia. Of the 63 patients who underwent EPS, 22 patients with inducible ventricular arrhythmia (17
EPISODES OF ARRHYTHMIA DURING THE HUTT.
patients) and 5 patients with prolonged HV intervals
Arrhythmias occurred during the HUTT in 29 of 41
>70 ms (2 with left bundle branch block, and 1 with
patients (71%) (Online Table 2). Bradyarrhythmias
bifascicular and 1 with trifascicular block) were
occurred as a part of the positive response in 12 pa-
excluded from the study. The final study population
tients (29.3%). Sinus bradycardia (with no pauses >3
consisted of 41 SHD patients with a history of syncope
s) was the most common arrhythmia seen in 7 pa-
and no inducible ventricular arrhythmia events (Figure 3). The mean age of the patients was 59 16 years (range:16 to 85 years), and the majority were males
tients (17.1%). Sinus pause of >3 s was documented in 5 patients (12.2%) with a mean pause duration of 3.6 0.53 s. The most common arrhythmia during the HUTT
with
was ectopic beats, which occurred in 14 patients
ischemic heart disease and 14 patients (34.1%) with
(34.1%). Ventricular ectopic beats were observed in
DCM. The mean LVEF was 42% 4.8% (range 30%
7 patients (17.07%), atrial ectopic beats in 3 patients
to 49%). The mean number of syncopal episodes was
(7.32%), and junctional ectopic beats in 3 patients
4.4 per year (range 3 to 7). Baseline parameters of
(7.32%). Three patients (7.32%) had tachyarrhythmias
the study population are summarized in Online
with atrial tachycardia seen in 2 patients (4.9%) dur-
Table 1.
ing the HUTT. The tachycardia rate varied between
(73.2%).
There
were
27
patients
(65.9%)
123 and 176 beats/min with a mean heart rate of 153 OUTCOME OF THE HUTT RESULTS. HUTT results
beats/min. The tachycardia lasted for 32 s in 1 patient
were positive in 25 of the 41 patients (61%); test re-
and 50 s in another and was asymptomatic and
sults were positive without pharmacological provo-
terminated spontaneously with no requirement for
cation in 6 of 25 patients (24%) and with NTG
cardioversion. Transient atrial fibrillation lasting for 3
provocation in 19 or 25 patients (76%). The most
min developed in 1 patient (2.4%) with a mean heart
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F I G U R E 3 Flowchart
*No syncope indicates 3 patients were lost to follow-up in group A and 2 in group B. No syncope was detected on telephone inquiry. HUTT ¼ head up tilt test; HV ¼ His to Ventricular; ILR ¼ insertable loop recorder; RS ¼ reflex syncope; VT ¼ Ventricular tachycardia.
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T A B L E 1 Pattern of Reflex Syncope on the Insertable Loop
Recorder
rate of 164 beats/min and normal blood pressure. Except for palpitations, there were no other specific complaints from the patient. There were no instances
Group A (n ¼ 17 of 21 [81%])
Group B (n ¼ 5 of 12 [41.7%])*
Type 1A
1 (5.9)
1 (20 [0])
1B
1 (5.9)
Type of Response
of ventricular tachyarrhythmias noted in any subjects during the HUTT. ILR OUTCOMES. Group A consisted of 21 of 25 pa-
Type 2A
4 (23.5)
2 (40 [0])
tients (84%) with positive HUTT results who under-
2B
5 (29.4)
0
went ILR implantation (Table 1). Group B consisted of
Type 3
6 (70.3)
2 (40)
12 of 16 patients (75%) with negative HUTT results
*One patient had syncope with intermittent atrioventricular block.
who underwent ILR implantation. Four patients in each group declined ILR placement.
F I G U R E 4 Correlation Between ILR and VASIS Responses
Correlation is shown between the HUTT response (VASIS) and the mechanism of syncope as documented by ILR (ISSUE3) in 17 patients with positive HUTT results. VASIS ¼ Vasovagal Syncope International Study; other abbreviations as in Figure 3.
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C ENTR AL I LL U STRA T I O N Approach to Syncope in Structural Heart Disease and Normal Holter and Negative EP Results
Syncope in SHD, Normal Holter, Negative EP study (N: 41)
Group A HUTT Positive (N: 25)
ILR Implanted 21
Syncope 17
Reflex Syncope 17
Group B HUTT Negative (N: 16)
ILR Implanted 12
ILR refused 4
Syncope 6
No Syncope 4
Reflex Syncope 5
Arrhythmic 0
ILR refused 4
No Syncope 6
Arrhythmic 1 (AV Block)
Shenthar, J. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. AV ¼ atrioventricular; EP ¼ electrophysiology; HUTT ¼ head up tilt test; ILR ¼ insertable loop recorder.
The mean duration of follow-up in ILR patients was 15 8 months. In group A patients, 17 of the 21
ms, and an AV Wenckebach 450-ms drive cycle length on EPS.
patients (81%) had syncope during follow-up. Of the
A comparison of the patients with positive HUTT
17 patients in group A, ILR recordings were sug-
results who had a syncopal episode during ILR
gestive of reflex syncope, with type 1A (Figure 1) in
(Figure 4) showed that, of the 4 patients with
1 of 17 patients (5.9%), type 1B in 1 of 17 patients
prolonged asystolic pause (VASIS type 2B) during
(5.9%), type 2A in 4 of 17 patients (23.5%), type 2B
HUTT, 1 patient had bradycardia with a decrease in
in 5 of 17 patients (29.4%), and type 3 in 6 of 17
heart rate >30% (ISSUE type 2A), and 2 patients had
patients (35.3%), according to the ISSUE classifica-
heart rate of <40 beats/min for >10 s (ISSUE type 2B)
tion. In group B, 5 of the 12 patients (41.7%) had ILR
during ILR.
recordings suggestive of reflex syncope, with type
During 15 8 months of follow-up, there were no
1A in 1 of 5 patients (20%), type 2A in 2 of 5 patients
significant ventricular or atrial tachyarrhythmias or
(40%), and type 3 in 2 of 5 patients (40%). One
deaths in either of the 2 ILR groups. Eight patients, 4
patient with coronary arterial disease in group B
in each group, refused ILR but continued to follow-
had intermittent complete AV block with no in-
up in the syncope clinic. In the patients who
crease in atrial rate, suggesting an AV conduction
refused ILR, syncope recurred in 2 of 4 patients (50%)
disease (Figure 2), and underwent permanent pace-
in group A and 1 of 4 patients (25%) in group B, with
maker implantation. The patient who developed
no deaths.
complete AV block had baseline right bundle branch
Three group A subjects and 2 group B patients were
block, normal axis, with a normal HV interval of 50
lost to follow-up. Telephone conversations revealed
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that they had no recurrences and were unwilling to
unknown cause with negative EPS, HUTT results were
come to the hospital.
positive in 57% of the cohort and that selective use of EPS, HUTT, and ILR resulted in a diagnosis in 78% of
DISCUSSION
patients. In the present study, 56% of patients had ILR findings most consistent with reflex syncope (see
The present study assessed causes and outcomes
criteria summarized above), with a higher incidence
of syncope in patients with SHD and negative
in those with a positive HUTT score (81%) compared
EPS. There were 4 principal observations. First,
to those with a negative HUTT score (50%). Results of
approximately 60% of patients in this study had
the present study agree with prior observations
positive HUTT results (Central Illustration). Second,
regarding the incidence of reflex syncope, even in
in patients with positive HUTT results, 81% had
SHD patients deemed to be at high risk (22).
findings suggestive of reflex syncope documented on
Furthermore, the medium-term mortality appears to
ILR. Third, in patients with negative HUTT results,
be low in SHD patients with negative EPS findings,
50% had ECG observations suggestive of reflex syn-
which is also consistent with the most common cause
cope on ILR. Finally, there were no deaths or clini-
of syncope, that is, the reflex syncope in origin
cally significant arrhythmia events detected during
(5,22,23).
follow-up, suggesting that the medium-term prog-
In the present study, of the 4 patients with
nosis is favorable in SHD patients and negative EPS
prolonged asystolic pause during the HUTT (VASIS
findings.
type 2B), 1 patient had bradycardia with a decrease
In syncope/collapse patients with SHD, a thorough
in heart rate >30% (ISSUE type 2A), and 2 patients
evaluation is essential to exclude cardiac causes. In
had a heart rate of <40 beats/min for >10 s (ISSUE
this regard, the presence of SHD does not necessarily
type 2B) during ILR (Figure 4). The findings from
imply that the syncopal event has a cardiac/
the present study differ from those reported in
arrhythmic cause with malignant connotation (5,10),
another study where 86% of patients with asystolic
but the latter is certainly a high priority to exclude,
pauses during the HUTT (VASIS type 2B) had
given the potential mortality risk. Nevertheless, pa-
asystolic pauses (ISSUE type 1) on ILR (24). In the
tients with underlying SHD can have nonarrhythmic
present study, there was no correlation between
causes of syncope, such as reflex or drug-induced
the HUTT response and ILR-documented syncope,
syncope/collapse (10,11).
and this is similar to what has been reported pre-
The HUTT is safe, inexpensive, and above all,
viously (25).
noninvasive. In addition, it has a relatively high diagnostic yield in the evaluation of syncope (3,12).
STUDY
However, most studies of HUTT (with or without
impact the interpretation of the findings reported
pharmacological provocation) have been conducted
here. First, the observations are derived from a small
in patients with structurally normal hearts (13–17).
number of patients at a single center. Furthermore,
As seen in the present study, however, even in
the study examined a highly select group of SHD
SHD patients, the Italian protocol procedure is safe,
patients with syncope and no documented or
unlike HUTT conducted with isoprenaline provo-
inducible arrhythmias. However, these are patients
cation, where significant episodes of arrhythmia
who would be otherwise classified as having syncope
can
infusion
of an unknown cause based on clinical guidelines and
Previous work suggests that approximately one-
lator. Second, the ambulatory monitoring to exclude
third of SHD patients with syncope/collapse have a
spontaneous episodes of arrhythmias prior to inclu-
reflex basis for their symptoms, and consequently,
sion in the study was of a relatively short duration
the HUTT may be useful as part of their overall
(24 h). A longer baseline monitoring period might
evaluation (4). Furthermore, it is suggested that the
have resulted in exclusion of additional patients.
HUTT may reasonably be used for evaluation of syn-
Third, in the present study, most of the patients had
cope in SHD patients with negative EPS findings
underlying coronary arterial disease, and further
(20,21).
studies in a larger number of patients with other
be
precipitated
with
isoprenaline
LIMITATIONS. A
number
of
limitations
would have qualified for implantation of a defibril-
(4,18,19).
Prolonged ILR ECG monitoring has become an
SHDs are needed. Fourth, the authors did not
invaluable tool in the evaluation of patients with
perform provocative testing with procainamide or
syncope of unknown origin. Garcia-Civera et al. (21)
flecainide as these were patients with SHD. Fifth, the
noted
results of the study do not apply to patients with
that,
in
SHD
patients
with
syncope
of
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Syncope in Structural Heart Disease
arrhythmias,
positive
EPS,
demon-
strable ischemia or EF <30%, and/or heart failure. Finally, the duration of ILR monitoring was only 15 8 months, and whether a more extended period of monitoring would have revealed a higher incidence of arrhythmic causes of syncope or greater mortality is not known.
PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: It is widely accepted that syncope/collapse in patients with structural heart disease (SHD) portends a worrisome prognosis. Potentially, this prognostic concern may lead physicians to more readily advise costly therapies, such as ablation, pacemakers, and implantable cardioverter-defibrillators. However, observations from the
CONCLUSIONS
present study remind clinicians that syncope in SHD patients may not be directly related to the SHD itself but often originates from
Reflex syncope is the most common cause of tran-
the lower risk reflex origin, comparable to the case in non-SHD
sient loss of consciousness in patients with SHD and
fainters. Consequently, prior to accepting SHD as being directly
a history of syncope/collapse, a negative EPS, and LV
responsible, all such patients merit careful assessment of the
dysfunction. Selective use of the HUTT and an ILR
multiple potential causes of syncope/collapse before clinicians
when needed, with clinical follow-up, appears to be
embark on a treatment strategy.
a useful diagnostic strategy and can be undertaken safely in this SHD patient population. However,
TRANSLATIONAL OUTLOOK: Current studies and practice
these results may not apply for patients with
guidelines appropriately emphasize the mortality risk associated
LVEF <30% and patients with heart failure.
with syncope in SHD patients. Without diminishing the value of such advice, the importance of substantiating a causal diagnosis
ADDRESS FOR CORRESPONDENCE: Prof. Jayaprakash
Shenthar,
Electrophysiology
Unit,
Department
of
Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, 9th Block Jayanagar, Bannerghatta
Road,
Bangalore
560069,
India.
E-mail:
must also be emphasized. To this end, the future of patient care should focus on the development and widespread use of novel remote cardiac monitoring technologies in order to establish with greater certainty the basis of syncope/collapse in individual patients.
[email protected].
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9. Brignole M, Moya A, Menozzi C, Garciacivera R, Sutton R. Proposed electrocardiographic classification of spontaneous syncope documented by an implantable loop recorder. Europace 2005;7:14–8. 10. Pezawas T, Stix G, Kastner J, Schneider B, Wolzt M, Schmidinger H. Implantable loop recorder in unexplained syncope: classification, mechanism, transient loss of consciousness and role of major depressive disorder in patients with and without structural heart disease. Heart 2007; 94:e17. 11. Arnar DO. Syncope in patients with structural heart disease. J Intern Med 2013;273:336–44. 12. Benditt DG, Ferguson DW, Grubb BP, et al. Tilt table testing for assessing syncope. J Am Coll Cardiol 1996;28:263–75. 13. Morillo CA, Klein GJ, Zandri S, Yee R. Diagnostic accuracy of a low-dose isoproterenol headup tilt protocol. Am Heart J 1995;129:901–6. 14. Flammang D, Erickson M, McCarville S, Church T, Hamani D, Donal E. Contribution of
15. Parry SW, Nath S, Bourke JP, Bexton RS, Kenny RA. Adenosine test in the diagnosis of unexplained syncope: marker of conducting tissue disease or neurally mediated syncope? Eur Heart J 2006;27:1396–400. 16. Raviele A, Menozzi C, Brignole M, et al. Value of head-up tilt testing potentiated with sublingual nitroglycerin to assess the origin of unexplained syncope. Am J Cardiol 1995;76:267–72. 17. Prabhu MA, Pillai V, Shenthar J. Comparison of efficacy, pattern of response, occurrence of arrhythmias, and the tolerability of nitroglycerine and isoprenaline as provocative drugs during head-up tilt test. Heart Lung Circ 2017;26: 586–92. 18. Leman RB, Clarke E, Gillette P. Significant complications can occur with ischemic heart disease and tilt table testing. Pacing Clin Electrophysiol 1999;22:675–7. 19. Kim PH, Ahn SJ, Kim JS. Frequency of arrhythmic events during head-up tilt testing in patients with suspected neurocardiogenic syncope or presyncope. Am J Cardiol 2004;94:1491–5.
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20. Zaidi A. Investigation of syncope: increasing the yield and reducing the cost. Eur Heart J 2000; 21:877–80. 21. Garcia-Civera R, Ruiz-Granell R, MorellCabedo S, et al. Selective use of diagnostic tests in patients with syncope of unknown cause. J Am Coll Cardiol 2003;41:787–90. 22. Merlos P, Rumiz E, Ruiz-Granell R, et al. Outcome of patients with syncope beyond the implantable loop recorder. Europace 2013;15: 122–6.
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23. Menozzi C, Brignole M, Garcia-Civera R, et al. Mechanism of syncope in patients with heart disease and negative electrophysiologic test. Circulation 2002;105:2741–5. 24. Brignole M, Menozzi C, Moya A, et al. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: third international study on syncope of uncertain cause (ISSUE-3): a randomized trial. Circulation 2012;125:2566–71. 25. Brignole M, Sutton R, Menozzi C, et al. Lack of correlation between the responses to tilt
testing and adenosine triphosphate test and the mechanism of spontaneous neurally mediated syncope. Eur Heart J 2006;27:2232–9.
KEY WORDS electrophysiology study, head-up tilt test, insertable loop recorder, structural heart disease, syncope
A PPE NDI X For supplemental tables, please see the online version of this paper.
VOL.
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ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study Jayaprakash Shenthar, MD, DM,a,b Mukund Aravind Prabhu, MD, DM,a,b Bharatraj Banavalikar, MD, DM,a,b David G. Benditt, MD,a,b Deepak Padmanabhan, MD, DMa,b
ABSTRACT OBJECTIVES This study sought to determine the cause of recurrent syncope and clinical outcomes by using the head up tilt test (HUTT) and an insertable loop recorder (ILR) in patients with structural heart disease (SHD) and negative electrophysiology study (EPS) results. BACKGROUND Patients with syncope and SHD with negative EPS findings have a low risk of sudden cardiac arrest. Nevertheless, the cause of recurrent syncope and the outcomes in these patients are not well characterized. METHODS AND RESULTS This prospective study evaluated syncope patients with SHD and negative EPS results by using HUTT (with sublingual nitroglycerine [NTG] provocation as needed) and ILR. A total of 41 SHD patients (27 patients [66%] had coronary arterial disease, and 14 patients [34.15%] had dilated cardiomyopathy with mean EF of 42% 4.8% [range 30% to 49%]) were included. HUTT findings were positive in 25 patients (61%) in group A and negative in 16 patients (39%) in group B. An ILR was implanted in 21 of 25 group A patients (84%) and in 12 of 16 group B patients (75%), and they were followed for 15 8 months. During follow-up, 17 of 21 patients (81%) in group A and 5 of 12 patients (41.7%) in group B had ILR evidence consistent with reflex syncope. One group B patient had documented atrioventricular block and underwent pacemaker implantation. There were no malignant ventricular arrhythmias or deaths on follow-up. CONCLUSIONS Reflex syncope is the most common cause of syncope and accounts for approximately 60% of cases in patients with SHD, negative EPS results, left ventricular systolic dysfunction with left ventricular EF >30%, and not in heart failure. (J Am Coll Cardiol EP 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.
S
yncope/collapse is a common clinical condition
syncope per se does not necessarily herald an adverse
and is among the most frequent diagnoses
prognosis if there is no documented ventricular
leading to emergency department visits and
arrhythmia (5). In fact, it is estimated that among SHD
hospital admissions (1–3). Furthermore, in patients
patients with syncope, approximately one-third,
who had syncope in the setting of a structurally
including those with inducible arrhythmia episodes,
normal heart, a vasovagal reflex mechanism is the
may have reflex syncope (4); however, substantial
most common diagnosis (4,5).
uncertainty remains.
As a rule, mortality risk is low in reflex syncope
This study used an insertable loop recorder (ILR) to
patients, especially those without structural heart
determine the cause of recurrent syncope and assess
disease (SHD). Their major concerns are risk of injury
subsequent clinical outcomes in syncope patients
and impact on quality of life (6). In patients with SHD,
with SHD, no previously documented ventricular
From the aElectrophysiology Unit, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, Karnataka, India; and the bUniversity of Minnesota Medical School, Minneapolis, Minnesota. Dr. Benditt is supported in part by a grant from the Dr. Earl E. Bakken Family for Heart-Brain research; and is a consultant for and holds equity in Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received September 13, 2018; revised manuscript received January 29, 2019, accepted January 31, 2019.
ISSN 2405-500X/$36.00
https://doi.org/10.1016/j.jacep.2019.01.021
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ABBREVIATIONS
arrhythmia episodes, negative electrophysi-
block documented either on ECG or 24-h Holter and
AND ACRONYMS
ology study (EPS) findings, and a positive
patients with implanted devices such as pacemakers,
head up tilt test (HUTT) score.
implantable cardioverter-defibrillators, and cardiac
DCM = dilated cardiomyopathy EF = ejection fraction
resynchronization therapy devices, or if the patient
METHODS
did not give consent for the study. Patients with
EPS = electrophysiological
bundle branch block or bifascicular or trifascicular
study
HUTT = head-up tilt test ILR = insertable loop recorder
The present study was undertaken prospec-
block with a prolonged His to ventricle interval >70
tively in SHD patients with a history of
ms, abnormal sinus node function (i.e., corrected
recurrent syncope, evaluated at the syncope
sinus node recovery time >550 ms) on EPS were
LV = left ventricle
clinic of a tertiary care cardiac center in south
excluded. Patients treated with nitrates were also
NTG = nitroglycerine
India.
excluded because nitrate tolerance potentially affects
SHD = structural heart disease
approved the study, and all subjects con-
The
institutional
review
board
sented to the study.
the response to NTG provocation during HUTT. HUTT INTERPRETATION. The modified Vasovagal
INCLUSION CRITERIA. Study subjects consisted of
Syncope International Study (VASIS) classification
consecutive patients with a history of syncope, with
was used to classify the syncopal events during the
moderate left ventricular (LV) dysfunction due to
HUTT (8). Briefly, the responses associated with a
coronary arterial disease or DCM, no documented
positive HUTT were:
spontaneous ventricular tachyarrhythmia episodes on 24-h Holter recording, and negative EPS findings. All study patients underwent a thorough clinical history examination, either from the patient or from eyewitnesses if present, or both if possible. A compre-
Type 1 (mixed): heart rate drops at the time of syncope with the ventricular rate not <40 beats/min or is <40 beats/min for <10 s with or without asystole of <3 s.
hensive physical examination included postural blood
Type 2A: cardio-inhibitory without asystole; heart
pressure recordings. Cardiovascular system assessment
rate falls to a ventricular rate <40 beats/min for
also included 12-lead electrocardiography (ECG) and an
>10 s, but asystole of >3 s does not occur.
echocardiogram (i.e., chamber dimensions, valvular
Type 2B: cardio-inhibitory with asystole; asystole occurs >3 s, and heart rate fall coincides with or
function, and LV ejection fraction [LVEF]). A staff electrophysiologist evaluated the 12-lead
precedes blood pressure fall.
ECG and the 24-h Holter recording obtained from all
Type 3: vasodepressor; heart rate does not drop
study subjects. Coronary angiography and, when
more than 10% from its peak, but at the time of
necessary, cardiac magnetic resonance, were used to
syncope blood pressure falls precipitously.
evaluate the presence and severity of coronary arterial disease, DCM, or other SHDs. Inducible ischemia was excluded in patients with ischemic heart disease by treadmill test, dobutamine stress test, or stress thallium scan. EPSs were undertaken in all patients, consisting of assessment of sinus node function and atrioventricular (AV) conduction during the EPS. Programmed stimulation was performed at 2 cycle lengths (600 and 450 ms), with up to 3 extra stimuli from the right ventricular apex and right ventricular outflow tract to assess for inducibility of tachyarrhythmia episodes at baseline and with an infusion of isoprenaline at 1 to 4 mg/min to achieve a heart rate of 110 to 120 beats/min. Patients with negative EPS
findings
underwent HUTT, using nitroglycerin (NTG) provocation if needed (i.e., the Italian protocol) (7).
CLASSIFICATION OF ARRHYTHMIC EVENTS DURING HUTT. Development of new arrhythmia episodes that
were not present during the 30-min observation and baseline tilt were documented. An arrhythmia event was defined as tachyarrhythmia if the heart rate was >100 beats/min after excluding sinus tachycardia. The criterion for bradyarrhythmia was sinus rate of <40 beats/min, development of junctional rhythm, pause >3 s, or any degree of AV block. The criterion for premature beats was a newly developed atrial, junctional, or ventricular ectopic heart beats. A new onset arrhythmia episode such as atrial fibrillation, atrial tachycardia, ventricular tachycardia, or ventricular fibrillation that occurred during the test was considered a significant arrhythmic event. IMPLANTATION
OF
AN
INSERTABLE
LOOP
EXCLUSION CRITERIA. Exclusion criteria included
RECORDER. Implantation of an ILR was offered to all
documented
tachyar-
patients with negative EPS findings with or without a
rhythmia episodes, inducible ischemia, LVEF <30%,
positive HUTT result. In those who agreed to the
presence
implantation, a Reveal XT insertable cardiac monitor
of
or
inducible
heart
failure,
ventricular significant
bradyar-
rhythmias such as sinus node dysfunction, or AV
(Medtronic
Inc.,
Minneapolis,
Minnesota)
was
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F I G U R E 1 ILR Recording Showing Type IA Response
Insertable loop recording from a 46-year-old male showing typical reflex syncope with a type 1A response. Note the typical sinus tachycardia at the beginning, following which is sinus bradycardia and then sinus arrest during the episode of syncope.
implanted subcutaneously in the left parasternal
Type 3: no or slight rhythm variation.
area. The ILR was programmed to save up to 3 manual
Type 4: tachycardia. Increase in heart rate >30% or
activations of 7.5 min. Automatic activations were
>120 beats/min.
programmed to a) rapid ventricular tachycardia (R-R interval: 260 ms in at least 30 of 40 consecutive beats); b) ventricular tachycardia (R-R interval: 261 to 340 ms in 16 consecutive beats); c) a pause of >3 s; or d) bradycardia (heart rate: 30 beats/min in 4 consecutive beats). ILR recordings were retrieved as soon as was feasible in case of syncope and assessed for any ventricular or atrial tachyarrhythmia, and the heart rate response during the episode. The International Study on Syncope of Uncertain Etiology (ISSUE) classification was used to document ECG syncope on ILR (9). Briefly, the classifications were as follows:
FOLLOW-UP. After patients received ILR implanta-
tion, they were followed in the outpatient clinic every 3 months until a diagnosis was reached or until the end of service of the device. Once the device reached its end of service, it was explanted with no further replacement. and patients were followed in the outpatient clinic. In those cases in which the patient refused ILR implantation, they were followed in the outpatient clinic. Endpoints were either syncope recurrence or mortality. STATISTICAL ANALYSIS. Data are presented as mean
Type 1: asystole with R-R pause >3 s (type 1A sinus
SD. Patients’ data were compared using Fisher’s
arrest, type 1B sinus bradycardia plus AV block,
exact test. Continuous variables were compared using
type 1C AV block).
Student t-test in the case of normal distribution
Type 2: bradycardia with decrease in heart rate
of values and the nonparametric Mann-Whitney
>30% (type 2A) or <40 beats/min for >10 s
U test in the case of an asymmetric distribution. A
(type 2B);
p value < 0.05 was considered significant.
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F I G U R E 2 Insertable Loop Recording From a Patient With Issue Type 1c Response
Note that there is no increase in atrial rate prior to the onset of sudden AV block, resulting in ventricular asystole with regular P waves and no QRS. AV ¼ atrioventricular; ISSUE ¼ International Study on Syncope of Uncertain Etiology.
RESULTS
common response was the modified VASIS type III noted in 13 patients (52%), type I in 6 patients (24%),
From January 2010 to June 2015, 70 patients who had
type 2B in 5 patients (20%), and type 2A in 1 patient
syncope with SHDs were evaluated. Seven patients
(4%). There was a good correlation between the
were excluded from the study because they had
clinical symptoms and HUTT-induced symptoms in
documented episodes of symptomatic ventricular
these patients.
arrhythmia. Of the 63 patients who underwent EPS, 22 patients with inducible ventricular arrhythmia (17
EPISODES OF ARRHYTHMIA DURING THE HUTT.
patients) and 5 patients with prolonged HV intervals
Arrhythmias occurred during the HUTT in 29 of 41
>70 ms (2 with left bundle branch block, and 1 with
patients (71%) (Online Table 2). Bradyarrhythmias
bifascicular and 1 with trifascicular block) were
occurred as a part of the positive response in 12 pa-
excluded from the study. The final study population
tients (29.3%). Sinus bradycardia (with no pauses >3
consisted of 41 SHD patients with a history of syncope
s) was the most common arrhythmia seen in 7 pa-
and no inducible ventricular arrhythmia events (Figure 3). The mean age of the patients was 59 16 years (range:16 to 85 years), and the majority were males
tients (17.1%). Sinus pause of >3 s was documented in 5 patients (12.2%) with a mean pause duration of 3.6 0.53 s. The most common arrhythmia during the HUTT
with
was ectopic beats, which occurred in 14 patients
ischemic heart disease and 14 patients (34.1%) with
(34.1%). Ventricular ectopic beats were observed in
DCM. The mean LVEF was 42% 4.8% (range 30%
7 patients (17.07%), atrial ectopic beats in 3 patients
to 49%). The mean number of syncopal episodes was
(7.32%), and junctional ectopic beats in 3 patients
4.4 per year (range 3 to 7). Baseline parameters of
(7.32%). Three patients (7.32%) had tachyarrhythmias
the study population are summarized in Online
with atrial tachycardia seen in 2 patients (4.9%) dur-
Table 1.
ing the HUTT. The tachycardia rate varied between
(73.2%).
There
were
27
patients
(65.9%)
123 and 176 beats/min with a mean heart rate of 153 OUTCOME OF THE HUTT RESULTS. HUTT results
beats/min. The tachycardia lasted for 32 s in 1 patient
were positive in 25 of the 41 patients (61%); test re-
and 50 s in another and was asymptomatic and
sults were positive without pharmacological provo-
terminated spontaneously with no requirement for
cation in 6 of 25 patients (24%) and with NTG
cardioversion. Transient atrial fibrillation lasting for 3
provocation in 19 or 25 patients (76%). The most
min developed in 1 patient (2.4%) with a mean heart
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F I G U R E 3 Flowchart
*No syncope indicates 3 patients were lost to follow-up in group A and 2 in group B. No syncope was detected on telephone inquiry. HUTT ¼ head up tilt test; HV ¼ His to Ventricular; ILR ¼ insertable loop recorder; RS ¼ reflex syncope; VT ¼ Ventricular tachycardia.
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T A B L E 1 Pattern of Reflex Syncope on the Insertable Loop
Recorder
rate of 164 beats/min and normal blood pressure. Except for palpitations, there were no other specific complaints from the patient. There were no instances
Group A (n ¼ 17 of 21 [81%])
Group B (n ¼ 5 of 12 [41.7%])*
Type 1A
1 (5.9)
1 (20 [0])
1B
1 (5.9)
Type of Response
of ventricular tachyarrhythmias noted in any subjects during the HUTT. ILR OUTCOMES. Group A consisted of 21 of 25 pa-
Type 2A
4 (23.5)
2 (40 [0])
tients (84%) with positive HUTT results who under-
2B
5 (29.4)
0
went ILR implantation (Table 1). Group B consisted of
Type 3
6 (70.3)
2 (40)
12 of 16 patients (75%) with negative HUTT results
*One patient had syncope with intermittent atrioventricular block.
who underwent ILR implantation. Four patients in each group declined ILR placement.
F I G U R E 4 Correlation Between ILR and VASIS Responses
Correlation is shown between the HUTT response (VASIS) and the mechanism of syncope as documented by ILR (ISSUE3) in 17 patients with positive HUTT results. VASIS ¼ Vasovagal Syncope International Study; other abbreviations as in Figure 3.
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C ENTR AL I LL U STRA T I O N Approach to Syncope in Structural Heart Disease and Normal Holter and Negative EP Results
Syncope in SHD, Normal Holter, Negative EP study (N: 41)
Group A HUTT Positive (N: 25)
ILR Implanted 21
Syncope 17
Reflex Syncope 17
Group B HUTT Negative (N: 16)
ILR Implanted 12
ILR refused 4
Syncope 6
No Syncope 4
Reflex Syncope 5
Arrhythmic 0
ILR refused 4
No Syncope 6
Arrhythmic 1 (AV Block)
Shenthar, J. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. AV ¼ atrioventricular; EP ¼ electrophysiology; HUTT ¼ head up tilt test; ILR ¼ insertable loop recorder.
The mean duration of follow-up in ILR patients was 15 8 months. In group A patients, 17 of the 21
ms, and an AV Wenckebach 450-ms drive cycle length on EPS.
patients (81%) had syncope during follow-up. Of the
A comparison of the patients with positive HUTT
17 patients in group A, ILR recordings were sug-
results who had a syncopal episode during ILR
gestive of reflex syncope, with type 1A (Figure 1) in
(Figure 4) showed that, of the 4 patients with
1 of 17 patients (5.9%), type 1B in 1 of 17 patients
prolonged asystolic pause (VASIS type 2B) during
(5.9%), type 2A in 4 of 17 patients (23.5%), type 2B
HUTT, 1 patient had bradycardia with a decrease in
in 5 of 17 patients (29.4%), and type 3 in 6 of 17
heart rate >30% (ISSUE type 2A), and 2 patients had
patients (35.3%), according to the ISSUE classifica-
heart rate of <40 beats/min for >10 s (ISSUE type 2B)
tion. In group B, 5 of the 12 patients (41.7%) had ILR
during ILR.
recordings suggestive of reflex syncope, with type
During 15 8 months of follow-up, there were no
1A in 1 of 5 patients (20%), type 2A in 2 of 5 patients
significant ventricular or atrial tachyarrhythmias or
(40%), and type 3 in 2 of 5 patients (40%). One
deaths in either of the 2 ILR groups. Eight patients, 4
patient with coronary arterial disease in group B
in each group, refused ILR but continued to follow-
had intermittent complete AV block with no in-
up in the syncope clinic. In the patients who
crease in atrial rate, suggesting an AV conduction
refused ILR, syncope recurred in 2 of 4 patients (50%)
disease (Figure 2), and underwent permanent pace-
in group A and 1 of 4 patients (25%) in group B, with
maker implantation. The patient who developed
no deaths.
complete AV block had baseline right bundle branch
Three group A subjects and 2 group B patients were
block, normal axis, with a normal HV interval of 50
lost to follow-up. Telephone conversations revealed
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that they had no recurrences and were unwilling to
unknown cause with negative EPS, HUTT results were
come to the hospital.
positive in 57% of the cohort and that selective use of EPS, HUTT, and ILR resulted in a diagnosis in 78% of
DISCUSSION
patients. In the present study, 56% of patients had ILR findings most consistent with reflex syncope (see
The present study assessed causes and outcomes
criteria summarized above), with a higher incidence
of syncope in patients with SHD and negative
in those with a positive HUTT score (81%) compared
EPS. There were 4 principal observations. First,
to those with a negative HUTT score (50%). Results of
approximately 60% of patients in this study had
the present study agree with prior observations
positive HUTT results (Central Illustration). Second,
regarding the incidence of reflex syncope, even in
in patients with positive HUTT results, 81% had
SHD patients deemed to be at high risk (22).
findings suggestive of reflex syncope documented on
Furthermore, the medium-term mortality appears to
ILR. Third, in patients with negative HUTT results,
be low in SHD patients with negative EPS findings,
50% had ECG observations suggestive of reflex syn-
which is also consistent with the most common cause
cope on ILR. Finally, there were no deaths or clini-
of syncope, that is, the reflex syncope in origin
cally significant arrhythmia events detected during
(5,22,23).
follow-up, suggesting that the medium-term prog-
In the present study, of the 4 patients with
nosis is favorable in SHD patients and negative EPS
prolonged asystolic pause during the HUTT (VASIS
findings.
type 2B), 1 patient had bradycardia with a decrease
In syncope/collapse patients with SHD, a thorough
in heart rate >30% (ISSUE type 2A), and 2 patients
evaluation is essential to exclude cardiac causes. In
had a heart rate of <40 beats/min for >10 s (ISSUE
this regard, the presence of SHD does not necessarily
type 2B) during ILR (Figure 4). The findings from
imply that the syncopal event has a cardiac/
the present study differ from those reported in
arrhythmic cause with malignant connotation (5,10),
another study where 86% of patients with asystolic
but the latter is certainly a high priority to exclude,
pauses during the HUTT (VASIS type 2B) had
given the potential mortality risk. Nevertheless, pa-
asystolic pauses (ISSUE type 1) on ILR (24). In the
tients with underlying SHD can have nonarrhythmic
present study, there was no correlation between
causes of syncope, such as reflex or drug-induced
the HUTT response and ILR-documented syncope,
syncope/collapse (10,11).
and this is similar to what has been reported pre-
The HUTT is safe, inexpensive, and above all,
viously (25).
noninvasive. In addition, it has a relatively high diagnostic yield in the evaluation of syncope (3,12).
STUDY
However, most studies of HUTT (with or without
impact the interpretation of the findings reported
pharmacological provocation) have been conducted
here. First, the observations are derived from a small
in patients with structurally normal hearts (13–17).
number of patients at a single center. Furthermore,
As seen in the present study, however, even in
the study examined a highly select group of SHD
SHD patients, the Italian protocol procedure is safe,
patients with syncope and no documented or
unlike HUTT conducted with isoprenaline provo-
inducible arrhythmias. However, these are patients
cation, where significant episodes of arrhythmia
who would be otherwise classified as having syncope
can
infusion
of an unknown cause based on clinical guidelines and
Previous work suggests that approximately one-
lator. Second, the ambulatory monitoring to exclude
third of SHD patients with syncope/collapse have a
spontaneous episodes of arrhythmias prior to inclu-
reflex basis for their symptoms, and consequently,
sion in the study was of a relatively short duration
the HUTT may be useful as part of their overall
(24 h). A longer baseline monitoring period might
evaluation (4). Furthermore, it is suggested that the
have resulted in exclusion of additional patients.
HUTT may reasonably be used for evaluation of syn-
Third, in the present study, most of the patients had
cope in SHD patients with negative EPS findings
underlying coronary arterial disease, and further
(20,21).
studies in a larger number of patients with other
be
precipitated
with
isoprenaline
LIMITATIONS. A
number
of
limitations
would have qualified for implantation of a defibril-
(4,18,19).
Prolonged ILR ECG monitoring has become an
SHDs are needed. Fourth, the authors did not
invaluable tool in the evaluation of patients with
perform provocative testing with procainamide or
syncope of unknown origin. Garcia-Civera et al. (21)
flecainide as these were patients with SHD. Fifth, the
noted
results of the study do not apply to patients with
that,
in
SHD
patients
with
syncope
of
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Syncope in Structural Heart Disease
arrhythmias,
positive
EPS,
demon-
strable ischemia or EF <30%, and/or heart failure. Finally, the duration of ILR monitoring was only 15 8 months, and whether a more extended period of monitoring would have revealed a higher incidence of arrhythmic causes of syncope or greater mortality is not known.
PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: It is widely accepted that syncope/collapse in patients with structural heart disease (SHD) portends a worrisome prognosis. Potentially, this prognostic concern may lead physicians to more readily advise costly therapies, such as ablation, pacemakers, and implantable cardioverter-defibrillators. However, observations from the
CONCLUSIONS
present study remind clinicians that syncope in SHD patients may not be directly related to the SHD itself but often originates from
Reflex syncope is the most common cause of tran-
the lower risk reflex origin, comparable to the case in non-SHD
sient loss of consciousness in patients with SHD and
fainters. Consequently, prior to accepting SHD as being directly
a history of syncope/collapse, a negative EPS, and LV
responsible, all such patients merit careful assessment of the
dysfunction. Selective use of the HUTT and an ILR
multiple potential causes of syncope/collapse before clinicians
when needed, with clinical follow-up, appears to be
embark on a treatment strategy.
a useful diagnostic strategy and can be undertaken safely in this SHD patient population. However,
TRANSLATIONAL OUTLOOK: Current studies and practice
these results may not apply for patients with
guidelines appropriately emphasize the mortality risk associated
LVEF <30% and patients with heart failure.
with syncope in SHD patients. Without diminishing the value of such advice, the importance of substantiating a causal diagnosis
ADDRESS FOR CORRESPONDENCE: Prof. Jayaprakash
Shenthar,
Electrophysiology
Unit,
Department
of
Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, 9th Block Jayanagar, Bannerghatta
Road,
Bangalore
560069,
India.
E-mail:
must also be emphasized. To this end, the future of patient care should focus on the development and widespread use of novel remote cardiac monitoring technologies in order to establish with greater certainty the basis of syncope/collapse in individual patients.
[email protected].
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KEY WORDS electrophysiology study, head-up tilt test, insertable loop recorder, structural heart disease, syncope
A PPE NDI X For supplemental tables, please see the online version of this paper.