Syncope: A Diagnostic and Treatment Strategy

Syncope
A Diagnostic and
Treatment Strategy
Presentation Overview
I. Prevalence & Impact

II. Etiology
III. Diagnosis & Evaluation Options
IV. Specific Conditions
V. Treatment Options
VI. Insights into more efficient and effective
diagnosis and treatment of patients with
syncope
Section I:
Prevalence and Impact

The Significance of Syncope
The only difference between

syncope and sudden death
is that in one you wake up.1
1 Engel GL. Psychologic stress, vasodepressor syncope, and sudden death. Ann Intern Med 1978; 89: 403-412.
1 National Disease and Therapeutic Index on Syncope and Collapse, ICD-9-CM 780.2, IMS America, 1997
2 Blanc J-J, L’her C, Touiza A, et al. Eur Heart J, 2002; 23: 815-820.
3 Day SC, et al, AM J of Med 1982
4 Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69:160-175
Syncope
Reported Frequency
 Individuals <18 yrs 15%
 Military Population 17- 46 yrs 20-25%
 Individuals 40-59 yrs* 16-19%
 Individuals >70 yrs* 23%

*during a 10-year period
Brignole M, Alboni P, Benditt DG, et al. Eur Heart J, 2001; 22: 1256-1306.
infrequent,
unexplained:
38% to 47% 1-4
explained:
53% to 62%
 500,000 new syncope patients each year 5

 170,000 have recurrent syncope 6
 70,000 have recurrent, infrequent, unexplained
syncope 1-4
1Kapoor W, Med. 1990;69:160-175. 4 Kapoor W, et al. N Eng J Med. 1983;309:197-204.
2 Silverstein M, et al. JAMA. 1982;248:1185-1189. 5 National Disease and Therapeutic Index, IMS America, Syncope and Collapse #780.2; Jan 1997-Dec 1997.
3 Martin G, et al. Ann Emerg. Med. 1984;12:499-504. 6 Kapoor W, et al. Am J Med. 1987;83:700-708.
 Some causes of syncope are potentially fatal
 Cardiac causes of syncope have the highest mortality
rates
25%
20%
Syncope Mortality
15%
10%
5%
0%
Overall Due to Cardiac Causes
1 Day SC, et al. Am J of Med 1982;73:15-23.
2 Kapoor W. Medicine 1990;69:160-175.
3 Silverstein M, Sager D, Mulley A. JAMA. 1982;248:1185-1189.
4 Martin G, Adams S, Martin H. Ann Emerg Med. 1984;13:499-504.

Impact of Syncope
100%
73% 1 71% 2
80%
60% 2
60%
37% 2
40%
20%
0%
Anxiety/ Alter Daily Restricted Change
Depression Activities Driving Employment
1Linzer, J Clin Epidemiol, 1991.

2Linzer, J Gen Int Med, 1994.
Sudden Death in the Allegheny
County, Pennsylvania
 Analysis of 1,216 death certificates during
1985-1986 of white males aged 35-44
years.
 786 due to coronary artery disease
 628 of 786 sudden (within 24 hour) death
 51.5% of CHD sudden death in subjects
without previous history of heart disease
Kuller LH. et al. Circulation 1989

Sudden Unexpected Death in the
Framingham Heart Study
 Sudden Unexpected Death 22-23% of all CHD
deaths
 Incidence of Sudden Unexpected Death:
15,1 / 10,000 / year in men
5,3 / 10,000/ year in women
 Predictor of Sudden Unexpected Death:
LVH by ECG, age, serum cholesterol, smoking
Schatzkin A et al. Am Heart J , 1984
Risk for Sudden Death in
Middle-Aged British Men
 7,735 men, aged 40-59 years f.u. 8 years
 117 sudden cardiac deaths (SCD)
 4.8 SCDs in 1,000/year with IHD
 1 SCD in 1,000/year without IHD
 Physical inactivity and smoking associated with
SCD only in absence of IHD
Wannamethee et al. Circulation 1995

Yearly Incidence of Sudden Death:
the Maastricht Study
 132,762 subjects age 20-75 years f.u. 4 years
 515 sudden cardiac arrests (SCA)
 History of cardiac disease 277 SCAs (54%)
 in 53% of women and 44% of men SCA was

the first manifestation of I.H.D.
De Vreede-Swagemakers et al. JACC 1997
Yearly Incidence of Sudden
Death:
 9.7 per 10,000 inhabitants
 57 per 10,000 in cardiac disease patients
 5 per 10,000 in subjects without history

of ischemic heart disease

Yearly Incidence of Sudden Death
 80% of SCAs at home
 60% of SCAs witnessed
 Cardiac resuscitation attempted in 51% of all
SCAs
 6% of 515 SCAs discharged alive from hospital
 Survival rates for witnessed SCA:
8% at home and 18% outside the home
Sudden Death in Italy from
ISTAT data
 160,000 cardiac attacks/year
 40,000 deaths
 20,000 out of hospital death
 10,000 sudden death (within 1

hour after onset of symptoms)
Unexpected Sudden Death in
Italy
• 45.000.000 people 20-75 years old

15.000 unexpected SD/year
(6.000 deaths for car accidents/year)
• 3.500.000 males age 55-65 years =

3.800 unexpected SD/year
Section II:
Etiology
Syncope:
A Symptom…Not a Diagnosis
 Self-limited loss of consciousness and

postural tone
 Relatively rapid onset
 Variable warning symptoms
 Spontaneous complete recovery
Rhythms During Recurrent Syncope
Bradycardia
36%
Normal Sinus
Rhythm
Normal Sinus Rhythm
58%
58%
Tachyarrhythmia
6%
Krahn A, et al. Circulation. 1999; 99: 406-410

Causes of Syncope1
Cause Prevalence Prevalence
(Mean) % (Range) %
Reflex-mediated:
Vasovagal 18 8-37
Situational 5 1-8
Carotid Sinus 1 0-4
Orthostatic hypotension 8 4-10
Medications 3 1-7
Psychiatric 2 1-7
Neurological 10 3-32
Organic Heart Disease 4 1-8
Cardiac Arrhythmias 14 4-38
Unknown 34 13-41
1Kapoor W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc:
1998; 1-13.
Syncope: Etiology
Structural Non-
Neurally- Cardiac
Orthostatic Cardio- Cardio-
Mediated Arrhythmia
Pulmonary vascular
1 2 3 4 5
• Vasovagal • Drug • Brady • Aortic
Sick sinus
• Psychogenic
• Carotid Induced Stenosis
AV block • Metabolic
Sinus • ANS • HOCM
• Tachy e.g. hyper-
• Situational Failure • Pulmonary
Cough Primary VT* ventilation
SVT Hypertension • Neurological
Post- Secondary
micturition • Long QT
Syndrome
24% 11% 14% 4% 12%
Unknown Cause = 34%

DG Benditt, UM Cardiac Arrhythmia Center
Causes of Syncope-like States
 Migraine*
 Acute hypoxemia*
 Hyperventilation*
 Somatization disorder (psychogenic syncope)
 Acute Intoxication (e.g., alcohol)
 Seizures
 Hypoglycemia
 Sleep disorders
* may cause ‘true’ syncope

Section III:
Diagnosis and
Evaluation Options
Syncope
Diagnostic Objectives
 Distinguish ‘True’ Syncope from other

‘Loss of Consciousness’ spells:
 Seizures
 Psychiatric disturbances
 Establish the cause of syncope with

sufficient certainty to:
 Assess prognosis confidently
 Initiate effective preventive treatment
Initial Evaluation
(Clinic/Emergency Dept.)
 Detailed history
 Physical examination
 12-lead ECG
 Echocardiogram (as available)
Syncope
Basic Diagnostic Steps
 Detailed History & Physical
 Document details of events
 Assess frequency, severity
 Obtain careful family history
 Heart disease present?

 Physical exam
 ECG: long QT, WPW, conduction system disease
 Echo: LV function, valve status, HOCM
 Follow a diagnostic plan...

Conventional Diagnostic Methods/Yield
Test/Procedure Yield
(based on mean time to diagnosis of 5.1 months7
History and Physical 49-85% 1, 2

(including carotid sinus massage)
ECG 2-11% 2
Electrophysiology Study without SHD* 11% 3
Electrophysiology Study with SHD 49% 3
Tilt Table Test (without SHD) 11-87% 4, 5
Ambulatory ECG Monitors:

 Holter 2% 7
 External Loop Recorder 20% 7

(2-3 weeks duration)
 Insertable Loop Recorder 65-88% 6, 7
(up to 14 months duration)
Neurological †
(Head CT Scan, Carotid Doppler) 0-4% 4,5,8,9,10
5 9 Day S, et al. Am J Med. 1982; 73: 15-23.

1 Kapoor, et al N Eng J Med, 1983. Kapoor, JAMA, 1992
6 10 Stetson P, et al. PACE. 1999; 22 (part II): 782.
2 Kapoor, Am J Med, 1991. Krahn, Circulation, 1995 * Structural Heart Disease
3 Linzer, et al. Ann Int. Med, 1997. 7 Krahn, Cardiology Clinics, 1997. † MRI not studied
4 Kapoor, Medicine, 1990. 8 Eagle K,, et al. The Yale J Biol and Medicine. 1983; 56: 1-8.
Syncope
Evaluation and Differential Diagnosis
History – What to Look for
 Complete Description
 From patient and observers
 Type of Onset
 Duration of Attacks
 Posture
 Associated Symptoms
 Sequelae
12-Lead ECG
 Normal or Abnormal?
 Acute MI
 Severe Sinus Bradycardia/pause
 AV Block
 Tachyarrhythmia (SVT, VT)
 Preexcitation (WPW), Long QT, Brugada
 Short sampling window (approx. 12 sec)

Carotid Sinus Massage
 Site:
Carotid arterial pulse just below thyroid cartilage
 Method:
 Right followed by left, pause between
 Massage, NOT occlusion
 Duration: 5-10 sec
 Posture – supine & erect
Carotid Sinus Massage
 Outcome:
 3 sec asystole and/or 50 mmHg fall in systolic blood
pressure with reproduction of symptoms =
Carotid Sinus Syndrome (CSS)

 Contraindications
 Carotid bruit, known significant carotid arterial disease,
previous CVA, MI last 3 months
 Risks
 1 in 5000 massages complicated by TIA
Conventional Ambulatory ECG
Low Yield, Poor Symptom / Arrhythmia Concordance*
 8 studies, 2612 patients

 19% pts had symptoms with AECG
Only 4% had arrhythmia with symptoms
 79% pts were without symptoms

14% had arrhythmia despite absence of
symptoms
* ACC/AHA Task Force, JACC 1999;912-948
Ambulatory ECG
Method Comments
Holter (24-48 hours) Useful for frequent events
Event Recorder Useful for infrequent events

Limited value in sudden LOC
Loop Recorder Useful for infrequent events
Implantable type more
convenient (ILR)
Wireless (internet) In development
Event Monitoring
Head-up Tilt Test (HUT)
 Unmasks VVS
susceptibility
 Reproduces symptoms
 Patient learns VVS
warning symptoms
 Physician is better able
to give prognostic /
treatment advice
Tilt Table Response in Patient
with Neurally-Mediated
Syncope
Sra JS. Ann Intern Med. 1991;114:1013-1019

Head-Up Tilt Test (HUT)

Electroencephalogram
 Not a first line of testing

 Syncope from Seizures
 Abnormal in the interval
between two attacks – Epilepsy
 Normal – Syncope
®
Reveal Plus
Insertable Loop Recorder
Patient Activator Reveal® Plus ILR 9790 Programmer

Value of
Event
Recorder
in
Syncope
*Asterisk denotes
event marker
Linzer M. Am J Cardiol. 1990;66:214-219.

ILR Recordings*
56 yo woman with syncope
accompanied with seizures.
Infra-Hisian AV Block: Dual
chamber pacemaker
65 yo man with syncope

accompanied with brief
retrograde amnesia.
VT and VF: ICD and meds
*Medtronic data on file
Randomized Assessment of Syncope Trial
Unexplained Syncope
after history, physical exam, ECG, Holter
Low Risk (EF > 35%)
ILR
Usual care including:
External loop recorder
- + Tilt test, EPS and others
External loop recorder + -

Tilt test, EPS, others
Diagnosis ILR
Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.
RAST Methods
 Prospective randomized trial
 60 patients with unexplained syncope referred for cardiac
investigation
 Inclusion:
 Recurrent unexplained syncope
 Referred to the arrhythmia service for cardiac investigation
 No clinical diagnosis after history, physical, ECG and at least 24
hours of cardiac monitoring
 Exclusion:
 LVEF < 35%
 Unable to give informed consent
 Major morbidity precluding one year of follow-up

RAST Results
Unexplained Syncope
n=60
ILR Conventional
n=30 n=30
In Follow-up Diagnosed Undiagnosed Diagnosed Undiagnosed

n=3 n=14 n=13 n=6 n=24

RAST Crossover Results
Unexplained Syncope
n=60
13/30 24/30
Undiagnosed after monitoring Undiagnosed after conventional
6 accepted crossover to conventional 21 accepted crossover to ILR
Diagnosed Undiagnosed Diagnosed Undiagnosed In follow-up

n=1 n=5 n=8 n=5 n=8

RAST - Diagnoses
14
12
number of patients
10
ILR Conventional
8
0
Bradycardia Tachycardia Vasovagal Seizures
Conventional EP Testing in Syncope
 Limited utility in syncope evaluation
 Most useful in patients with structural heart

disease
 Heart disease……..50-80%
 No Heart disease…18-50%
 Relatively ineffective for assessing

bradyarrhythmias
Brignole M, Alboni P, Benditt DG, et al. Eur Heart Journal 2001; 22: 1256-1306.
EP Testing in Syncope:
Useful Diagnostic Observations
 Inducible monomorphic VT
 SNRT > 3000 ms or CSRT > 600 ms
 Inducible SVT with hypotension
 HV interval ≥ 100 ms (especially in
absence of inducible VT)
 Pacing induced infra-nodal block
ISSUE Study
International Study of Syncope of Uncertain Etiology
 Objectives:
• Understand the mechanism of syncope in tilt-positive and tilt-
negative (isolated) patients
• Use the ILR to assess the correlation of rhythms captured

during tilt testing and spontaneous recurrent episodes
 Inclusion Criteria:
• Patients with three or more syncopal episodes in the last 2
years
• Groups matched in age, sex, history of syncope, ECG, Echo

abnormalities, SHD and arrhythmias
Moya A. Circulation. 2001; 104:1261-1267

ISSUE Study Design
 Multicenter, prospective
111 syncope patients
3 episodes in 2 years, first and last episode >6 months apart
History, physical exam, ECG, CSM, echo,

Holter (24 hr), other tests as appropriate
Tilt test followed by implant of Reveal

Insertable Loop Recorder
Follow-up to recurrent spontaneous episode

ISSUE Study Results
Tilt-Negative Tilt-Positive
Results Syncope (Isolated) Syncope
n=82 n=29
Recurrent Event Occurrence (#) 34% (28) 34% (10)
Mean Time to Recurrent Event 105 days (47-226) 59 (22-98)
(range)
ILR ECG Documented (#) 29% (24) 28% (8)
Tachyarrhythmia 2% (2)
Bradycardia 16% (13) 21% (6)
–Sinus Brady 2% (2) 3% (1)
–Sinus Arrest 12% (10) 17% (5)
–AV Block 1% (1)
Total Arrhythmic 18% (15) 21% (6)
Normal Sinus Rhythm 11% (9) 7% (2)

ISSUE Study
 Conclusions:
• Homogeneous findings from tilt-negative and tilt-
positive syncope patients were observed (clinical
characteristics and outcomes). Most frequent finding
was asystole secondary to progressive sinus
bradycardia, suggesting a neuromediated origin
• In this study tilt-negative patients had as many

arrhythmias (18%) as tilt-positive patients (21%)
• In tilt-positive patients the spontaneous episode ECG

was more frequently asystolic than what was
predicted by tilt test

ISSUE Study Implications
 HUT outcome was not predictive of
vasodepressor vs. cardioinhibitory response
 Bradycardia is common in spontaneous VVS -
independent of HUT outcome
 Bradycardia is more prevalent in spontaneous
events vs. HUT induced VVS
• Clinical Implication: Consider a strategy of
postponing treatment until a spontaneous
episode can be documented

Symptom-Rhythm Correlation
Auto Activation
Point
Patient
Activation
Point
Diagnostic Limitations
 Difficult to correlate
spontaneous events and
laboratory findings
 Often must settle for an
attributable cause
 Unknowns remain 20-30% 1
1Kapoor W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc:
1998; 1-13.
Unexplained Syncope Diagnosis
History and Physical Exam
Surface ECG
ENT Evaluation Endocrine

Evaluation
CV Syncope
Workup
Neurological Other CV
Testing • Holter Testing
• Head CT Scan • ELR or ILR
• Angiogram
• Carotid Doppler • Tilt Table
• Exercise Test
• MRI • Echo
• SAECG
• Skull Films • EPS
• Brain Scan
• EEG
Psychological
Evaluation Adapted from: W.Kapoor.An overview of the evaluation
and management of syncope. From Grubb B, Olshansky B (eds)
Syncope: Mechanisms and Management.
Armonk, NY: Futura Publishing Co., Inc.1998.
Typical Cardiovascular Diagnostic Pathway
Syncope
History and Physical, ECG
Known No
SHD SHD
> 30 days; < 30 days

Echo
> 2 Events
EPS
Tilt
Tilt Holter/ ELR
- + ILR ILR
Adapted from:
Tilt/ILR Treat Linzer M, et al. Annals of Int Med, 1997. 127:76-86.
Syncope: Mechanisms and Management. Grubb B, Olshansky B (eds) Futura Publishing 1999
Zimetbaum P, Josephson M. Annals of Int Med, 1999. 130:848-856.
Krahn A et al. ACC Current Journal Review,1999. Jan/Feb:80-84.
Section IV:
Specific Conditions
Neurally-Mediated Reflex Syncope
(NMS)
 Vasovagal syncope (VVS)

 Carotid sinus syndrome (CSS)
 Situational syncope
 post-micturition
 cough
 swallow
 defecation
 blood drawing
 etc.
NM Reflex Syncope:
Pathophysiology
 Multiple triggers
 Variable
contribution of
vasodilatation and
bradycardia
NMS – Basic Pathophysiology
Feedback via
Cerebral Carotid Baroreceptors
Cortex Other Mechanoreceptors
Baro-
Parasympathetic (+) receptors
Heart
sympathetic (+) ¯ Heart Rate

¯ AV
Conduction
Vascular
Bed Bradycardia/
Hypotension
_
Vasodilatation
Benditt DG, Lurie KG, Adler SW, et al. Pathophysiology of vasovagal syncope. In: Neurally mediated syncope: Pathophysiology, investigations and treatment. Blanc
JJ, Benditt D, Sutton R. Bakken Research Center Series, v. 10. Armonk, NY: Futura, 1996
Vasovagal Syncope (VVS):
Clinical Pathophysiology
 Neurally Mediated Physiologic Reflex

Mechanism with two Components:
 Cardioinhibitory ( HR )
 Vasodepressor ( BP )
 Both components are usually present

Prevalence of VVS
 Prevalence is poorly known

 Various studies report 8% to 37% (mean 18%)
of cases of syncope (Linzer 1997)
 In general:
 VVS patients younger than CSS patients
 Ages range from adolescence to elderly
(median 43 years)
 Pallor, nausea, sweating, palpitations are common
 Amnesia for warning symptoms in older patients
Spontaneous VVS
16.3
sec
Continuous Tracing 1 sec

Management Strategies for VVS
 Optimal management strategies for VVS are a

source of debate
 Patient education, reassurance, instruction
 Fluids, salt, diet
 Tilt Training
 Support hose
 Drug therapies
 Pacing
 Class II indication for VVS patients with positive HUT and
cardioinhibitory or mixed reflex
VVS: Tilt-Training
 Objectives
 Enhance Orthostatic Tolerance
 Diminish Excessive Autonomic Reflex
Activity
 Reduce Syncope Susceptibility /
Recurrences
 Technique
 Prescribed Periods of Upright Posture
 Progressive Increased Duration
Carotid Sinus Syndrome (CSS)
 Syncope clearly associated with carotid

sinus stimulation is rare (≤1% of
syncope)
 CSS may be an important cause of

unexplained syncope / falls in older
individuals
Etiology of CSS
 Sensory nerve endings in the

carotid sinus walls respond to
deformation
 “Deafferentation” of neck muscles
may contribute
 Increased afferent signals to brain
stem
Carotid Sinus  Reflex increase in efferent vagal
activity and diminution of
sympathetic tone results in
bradycardia and vasodilation
Carotid Sinus Hypersensitivity(CSH)
 Abnormal response to CSM

 Absence of symptoms attributable to CSS
 CSH reported frequent in ‘fallers’ (Kenny)
CSH  CSS
CSS and Falls in the Elderly
 30% of people >65 yrs of age fall each year1

 Total is 9,000,000 people in USA
 Approximately 10% of falls in elderly persons are due to
syncope2
 50% of fallers have documented recurrence3

 Prevalence of CSS among frequent and
unexplained fallers unknown but…
 CSH present in 23% of >50 yrs fallers presenting at ER 3
1Fallingin the Elderly: U.S. Prevalence Data. Journal of the American Geriatric Society, 1995.
2 Campbell et al: Age and Aging 1981;10:264-270.
3Richardson DA, Bexton RS, et al. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting
to the Accident and Emergency Department with “unexplained” or “recurrent” falls. PACE 1997
Section V:
Treatment Options
VVS: Pharmacologic Rx
 Salt /Volume
 Salt tablets, ‘sport’ drinks, fludrocortisone
 Beta-adrenergic blockers
 1 positive controlled trial (atenolol),
 1 on-going RCT (POST)
 Disopyramide
 SSRIs
 1 controlled trial
 Vasoconstrictors (e.g., midodrine)

 1 negative controlled trial (etilephrine)
Midodrine for Neurocardiogenic Syncope
100
Symptom – Free Interval
80
60 Midodrine
Fluid
40
20
p < 0.001
0
0 20 40 60 80 100 120 140 160 180
Months
Journal of Cardiovascular Electrophysiology Vol. 12, No. 8, Perez-Lugones, et al.
Status of Pacing in VVS
 Perception of pacing for VVS changing:

 VVS with +HUT and cardioinhibitory response a Class IIb
indication1
 Recent clinical studies demonstrated benefits of

pacing in select VVS patients:
 VPS I
 VASIS
 SYDIT
 VPS II –Phase I
 ROME VVS Trial
1Gregoratos G, et al. ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmic Devices. Circulation. 1998; 97:
1325-1335.
Status of Pacing in VVS
 Benefits of specific device features

evolving:
 Some success with DDD/DDI hysteresis 1
• “False positives” may result in prolonged high rate intervention

• Tied to lower rate intervention
 Rate drop therapies designed for treating VVS syncope

appear to be successful 2-4
1 Sutton R, et al. Circulation. 2000; 102:294-299.

2 Connolly S, et al. J Am Coll Cardiol 1999; 33:16-20.
3 Ammirati F, et al. Circulation. 2002; 104: 52-57.
4 Ammirati F, et al. NASPE Abstract #307. PACE, Vol. 24, April 2002, Part II.
VPS-I
Vasovagal Pacemaker Study I
 Study Design:
54 patients randomized, prospective, single center
_ 27 DDD pacemaker with rate drop response (RDR)
_ 27 no pacemaker
 Patient Inclusion Criteria:

6 syncopal events ever
+HUT
Relative bradycardia*
*a trough heart rate <60/min if no isoproterenol used,

<70/min if up to 2 mcg/min isoproterenol used, or <80/min
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20. if over 2 mcg/min isoproterenol used
VPS- I
 Endpoints:
Time to first syncope
 Outcome:
PACEMAKER CONTROL
RESULTS (n= 27) (n=27)
Number of patients w/syncopal recurrence 6 (22%) 19 (70%)

Mean time to first recurrence (days) 112 54
Relative risk reduction of syncope* 85.4% -
*2p = 0.000022
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.

VPS- I
100
90
80 Control
(No Pacemaker)
70
60
Cumulative
Risk 50
(%) 2P=0.000022
40
30
Pacemaker
20
10
0
0 3 6 9 12 15
Time in Months
Number C 27 9 4 2 1 0
At Risk P 27 21 17 12 11 8

VPS-I
 Conclusion:
Dual-chamber pacing with rate drop response
reduces the likelihood of syncope in patients
with recurrent VVS.

VASIS
Vasovagal Syncope International Study
 Study Design:
 42 patients, randomized, prospective, multicenter
_ 19 DDI pacemaker (80 bpm) with rate hysteresis (45 bpm)
_ 23 no pacemaker

 > 3 syncopal events in 2 years and last event occurring within 6
months of enrollment and,
 Positive VASIS type 2A or 2B cardioinhibitory response to HUT
and,
 Age > 40 years or drug refractory if < 40 years
Sutton, R, et al. Circulation. 2000; 102:294-299.

VASIS
 Endpoints:
Time to first syncope
 Outcome:
No
Pacemaker Pacemaker
RESULTS
(n= 19) (n=23)

Median time to first recurrence (months)* 15 5
*P= 0.0006

VASIS
100 Pacemaker
% syncope-free
80
p=0.0004
60
40
No-Pacemaker
20
0 2 3 4 5 6
Years
# of
pts 40 31 23 15 14 12 7

VASIS
 Conclusion:
Dual-chamber pacing (at a rate of 80 bpm )
with rate hysteresis reduces the likelihood of
syncope in patients with tilt-positive,
cardioinhibitory syncope.

SYDIT
Syncope Diagnosis and Treatment Study
 Study Design:
93 patients randomized, prospective, multicenter
_ 47 Atenolol 100 MG/D

 > 55 yrs
> 3 syncopal episodes in 2 years
+ HUT with relative bradycardia (trough HR <60 bpm)
Ammirati F, et al. Circulation. 2001; 104:52-57.
SYDIT
 Endpoints:
 Time to first syncope
 Outcome:
PACED DRUG
RESULTS (n= 46) (n= 47)
Number of patients w/syncopal recurrence* 2 (4%) 12 (25%)
Median time to first recurrence (days) 390 135
*P=0.004
Ammirati, et al. Circulation. 2001; 104:52-57.

SYDIT
Syncope-free Survival: Intention-to-Treat (n=46/paced, 47/drug).
1.0
0.9
% of syncope free pts
drug
pacemaker
0.8 P = 0.0032
0.7
0.6
0 100 200 300 400 500 600 700 800 900 1000
Time (days)
SYDIT
 Conclusion:
Dual-chamber pacing + RDR is superior to Atenolol in
prevention of recurrent syncope in highly symptomatic
patients with relative bradycardia during tilt-induced
syncope.

VPS-II: Phase I
Vasovagal Pacemaker Study-II
 Study Design:
100 patients, randomized, prospective, multicenter
_ 50 ODO pacemaker (inactive mode)

> 6 syncope events ever or > 3 syncope events in
2 years or > 1 syncope event in 6 months and,
Positive HUT with syncope or presyncope and a
heart rate blood pressure product <9000
Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking
Clinical Trials, May 11, 2002.
VPS-II: Phase I
 Endpoints:
 Time to first syncope
 Outcome:
DDD Pacemaker ODO Pacemaker

RESULTS (n= 50) (n= 50)

Relative Risk Reduction* 28.7% -
*P=0.153
VPS-II: Phase I
0.4
0.3
Cumulative Risk of
ODO
DDD
Syncope
0.2
P = 0.153 (one-sided)
0.1
0.0
0 1 2 3 4 5 6
Number at Risk ODO 40 37 35 32 31 21

DDD 39 36 34 33 33 17
VPS-II: Phase I
 Conclusions:
 Lower than anticipated syncope event rate in the
control arm.
 Higher than anticipated event rate in the treatment
group.
 Consequence: treatment effect was less than VPS-I.
 Results favored pacing but the treatment effect was
not statistically significant.
VVS Pacing Trials Conclusions
DDD pacing reduces the risk of syncope

in patients with recurrent, refractory,
highly-symptomatic, cardioinhibitory
vasovagal syncope.
SAFE PACE Study Design
 Randomized controlled trial (N=175):

 Pacing (87) vs. No Pacing (88)
 Single center: Royal Victoria Infirmary,

Newcastle, UK
 Recruitment began: April 1998
 12 month follow-up per patient
 Study concluded: May 2000
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
SAFE PACE Inclusion Criteria
 Consecutive adults attending accident

and emergency department
• > 50 Years
- Experienced non-accidental fall
• Positive response to CSM

SAFE PACE Screening Process
Accident and Emergency Attendees > 50 Yrs
Falls or Syncope
Non-accidental Fall
CSM Performed
Cardioinhibitory or Mixed CSH
RCT
Control Pacemaker

SAFE PACE Screening Results
RCT (n=175)
Control Pacemaker
(n=88) (n=87)
• No pacing intervention • Medtronic Thera DR
(Rate Drop Response
Algorithm)

SAFE PACE Results
Number of Falls
Control Pacemaker
n=87 n=84
% Participants 60% 58%
w/Falls
70%
Total Number of 699 216
Falls* Reduction
[OR 0.42; 95%
CI: 0.23, 0.75]
Mean Number of 9.3 4.1
Falls**
* Falls during 12 months post randomization

** Crude adjustment calculation

SAFE PACE Results
Number of Syncopal Episodes
Control Pacemaker
N=87 N=84
% Participants 22% 11%

w/Syncopal Events
Total Number of 47 22 50%

Syncopal Events Reduction
[OR 0.53; 95%
Mean Number Syncopal 1.14 0.20 CI 0.23; 1.20 ns]
Events
* Syncopal events 12 months past randomization

** Crude adjustment calculation

SAFE PACE Results
Number of Injury Events
Control Pacemaker
n= 87 n= 84
% Participants w/Injurious 41% 35%
Events
Total Number Injury 202 61

Events
70%
Reduction
-Fractures 4 3
-Soft Tissue Injury 198 58
* Injurious events 12 months post randomization

SAFE PACE Conclusions
In patients with unexplained falls and a

diagnosis of Cardioinhibitory CSH, cardiac
pacing reduced the total number of:
 Falls by 70%
 Syncopal events by 53%
 Injurious events by 70%

Role of Pacing in CSS --
Syncope Recurrence Rate
75% Class I indication for
pacing (AHA and BPEG)
57%
Limit pacing to CSS that
50% is:
•Cardioinhibitory
•Mixed
25% %6
DDD/DDI superior to VVI
(Mean follow-up = 6 months)
0%
No Pacing Pacing
Brignole et. Al. Diagnosis, natural history and treatment. Eur JCPE. 1992; 4:247-254
Section VI:
Insights into More Efficient and

Effective Diagnosis and Treatment
Principal Causes of
Orthostatic Syncope
 Drug-induced (very common)
 diuretics
 vasodilators
 Primary autonomic failure

 multiple system atrophy
 Parkinsonism
 Secondary autonomic failure

 diabetes
 alcohol
 amyloid
 Alcohol
 orthostatic intolerance apart from neuropathy
Syncope Due to Arrhythmia or
Structural CV Disease:
General Rules
 Often life-threatening and/or exposes
patient to high risk of injury
 May be warning of critical CV disease
 Aortic stenosis, Myocardial ischemia, Pulmonary
hypertension
 Assess culprit arrhythmia / structural

abnormality aggressively
 Initiate treatment promptly
Principal Causes of Syncope due to
Structural Cardiovascular Disease
 Acute MI / Ischemia
 Acquired coronary artery disease
 Congenital coronary artery anomalies
 HOCM
 Acute aortic dissection
 Pericardial disease / tamponade
 Pulmonary embolus / pulmonary
hypertension
 Valvular abnormalities
 Aortic stenosis, Atrial myxoma
Syncope Due to Cardiac Arrhythmias
 Bradyarrhythmias
 Sinus arrest, exit block
 High grade or acute complete AV block
 Tachyarrhythmias
 Atrial fibrillation / flutter with rapid ventricular
rate (e.g. WPW syndrome)
 Paroxysmal SVT or VT
 Torsades de pointes
Conclusion
Syncope is a common symptom,

often with dramatic consequences,
which deserves thorough investigation
and appropriate treatment of its cause.
AECG: 74 yr Male, Syncope
From the files of DG Benditt, UM Cardiac Arrhythmia Center

Syncope: Torsades

28 yo man in the ER multiple
times after falls resulting in
trauma
VT: ablated and medicated
83 yo woman
Bradycardia: Pacemaker
implanted
Reveal ® ILR recordings; Medtronic data on file.

Infra-His Block

Drug-Induced QT Prolongation
 Antiarrhythmics
 Class IA ...Quinidine, Procainamide, Disopyramide
 Class III…Sotalol, Ibutilide, Dofetilide, Amiodarone, (NAPA)
 Antianginal Agents
 (Bepridil)
 Psychoactive Agents
 Phenothiazines, Amitriptyline, Imipramine, Ziprasidone
 Antibiotics
 Erythromycin, Pentamidine, Fluconazole
 Nonsedating antihistamines
 (Terfenadine), Astemizole
 Others
 (Cisapride), Droperidol
Treatment of Syncope Due to
Bradyarrhythmia
 Class I indication for pacing using dual-

chamber system wherever adequate
atrial rhythm is available
 Ventricular pacing in atrial fibrillation
with slow ventricular response
Treatment of Syncope Due to
Tachyarrhythmia
 Atrial Tachyarrhythmias;
 AVRT due to accessory pathway – ablate pathway
 AVNRT – ablate AV nodal slow pathway
 Atrial fib– Pacing, linear / focal ablation, ICD selected pts
 Atrial flutter – Ablation of reentrant circuit
 Ventricular Tachyarrhythmias;
 Ventricular tachycardia – ICD or ablation where appropriate
 Torsades de Pointes – withdraw offending Rx or ICD (long-
QT/Brugada)
 Drug therapy may be an alternative in many

cases
Additional Slides
Falls -- Incidence, Recurrence, CHS*
75%
50% 1
50%
30% 1
23% 2
25%
0%
Incidence Recurrence CSH* present
> 65 yrs. old in fallers > 50 yrs.
presenting at ER
1 Falling in the Elderly, 1995.
2 Richardson, PACE, 1997.
* Carotid Sinus Hypersensitivity
VVS Pacing Trials
Comparison Summary
Pacing in VVS
Two randomized, controlled trials

suggest benefit in selected patients with
multiple (>5 lifetime) syncope
recurrences and one or more of:
prominent cardioinhibitory features
asystolic pause >10 seconds
sustained HR<40/minute
VVS Recurrences
 35% of patients report syncope
recurrence during follow-up ≤3
years
 Positive HUT with >6 lifetime
syncope episodes: recurrence risk
>50% over 2 years
Sheldon et al. Circulation 1996; 93: 973-81.

Savage et al. STROKE 1985; 16: 626-29.
SAFE PACE 2:
Syncope and Falls in the Elderly
 30% of individuals >65 yrs fall each year
 5% of falls result in fractures
 1% of falls result in hip fractures
 SAFEPACE Pilot Study
18% prevalence of CSH in
unexplained ‘fallers’
31% in ‘fallers’ >80 yrs
Rate Drop Response Overview
Detection Options
Drop Low Rate

Both
Detect Detect
Detects relative Detection occurs Detects heart

heart rate drops when either Drop rate that falls to
of a pre- Detection or Low a user-defined
determined size Rate Detection lower rate
criteria are met
Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Drop Detection with Intervention
Drop Detection Method: Drop Size 25, Drop Rate 70
110
100 Peak Rate=90 bpm
90
Ventricular Rate
80
Drop Size=25 bpm
70 Drop Rate
60
2 consecutive beats < Drop
50
Size and Drop Rate
40

Drop Detect Peak Rate
Drop Detection Method: Drop Size 25

120
110 Peak Rate=90 bpm

100
Ventricular Rate
90
80
Drop Size=25
70 bpm
60
50
40

Low Rate Detect
Low Rate Detection Method: Lower Rate 40, Detection beats 2
110
100
90
Ventricular Rate
80
70
60 2 consecutive paced
beats at Lower Rate
50
40
Lower Rate
30

Using Both Detection Algorithms
 When both detection algorithms are

used:
 Detection occurs when either Drop Detection
or Low Rate Detection criteria are met
 Intervention Rate, Duration and Termination
are programmed the same as when using the
individual detection modes

Rate Drop Intervention Therapy
 DDD or DDI pacing

 Pacing intervention
 Paces at programmed Intervention Rate for
programmed duration
 Pacing termination
 Pacing rate decreases until there are three
consecutive atrial senses or Lower Rate is
reached

Challenges of Syncope
 Cost
 Cost/year
 Cost/diagnosis
 Quality of Life Implications

 Work/financial
 Mobility (automobiles)
 Psychological
 Diagnosis & Treatment

 Diagnostic yield and repeatability of tests
 Frequency and clustering of events
 Difficulty in managing/treating/controlling future events
 Appropriate risk stratification
 Complex Etiology
Diagnosing VVS
 Patient history and physical exam

 Positive tilt table test
(ACC Consensus Protocol)
 Overnight fast
 ECG
 Blood pressure 60° - 80°
 Supine and upright
 Tilt to 60-80 degrees
 Isoproterenol
 Re-tilt
DG Benditt, Tilt Table Testing, 1996.

VVS: Treatment Overview
 Education
 symptom recognition
 reassurance
 situation avoidance
 Tilt-Training
 prescribed upright posture
 Pharmacologic Agents
 salt/volume management
 beta-adrenergic blockers
 SSRIs
 vasoconstrictors (e.g., midodrine)
 Cardiac Pacemakers
Tilt-Training: Clinical Outcomes
 42 HUT positive (21±13 min) VVS patients

 Home training: two 30 minute sessions daily
 Outcomes
 41/42 pts --->45 min asymptomatic HUT
 Clinical follow-up: 15.1±7.8 mos
• 36 pts syncope free
• 4 pts: presyncope
• 1 pt: syncope recurrences
Reybrouck et al. PACE 2000; 23:493-8

Syncope: A Diagnostic and Treatment Strategy

Enviado por

Dados do documento

Título original

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

Syncope: A Diagnostic and Treatment Strategy

Enviado por

Direitos autorais:

Formatos disponíveis

Syncope

I. Prevalence & Impact

Prevalence and Impact

The only difference between

 Military Population 17- 46 yrs 20-25%

 Individuals 40-59 yrs* 16-19%

 Individuals >70 yrs* 23%

 500,000 new syncope patients each year 5

4 Martin G, Adams S, Martin H. Ann Emerg Med. 1984;13:499-504.

1Linzer, J Clin Epidemiol, 1991.

Kuller LH. et al. Circulation 1989

Wannamethee et al. Circulation 1995

 132,762 subjects age 20-75 years f.u. 4 years

 515 sudden cardiac arrests (SCA)

 History of cardiac disease 277 SCAs (54%)

 in 53% of women and 44% of men SCA was

 57 per 10,000 in cardiac disease patients

 5 per 10,000 in subjects without history

De Vreede-Swagemakers et al. JACC 1997

 160,000 cardiac attacks/year

 20,000 out of hospital death

 10,000 sudden death (within 1

• 45.000.000 people 20-75 years old

• 3.500.000 males age 55-65 years =

 Self-limited loss of consciousness and

Krahn A, et al. Circulation. 1999; 99: 406-410

Unknown Cause = 34%

* may cause ‘true’ syncope

 Distinguish ‘True’ Syncope from other

 Establish the cause of syncope with

 Heart disease present?

 Follow a diagnostic plan...

History and Physical 49-85% 1, 2

Electrophysiology Study without SHD* 11% 3

Electrophysiology Study with SHD 49% 3

Tilt Table Test (without SHD) 11-87% 4, 5

Ambulatory ECG Monitors:

 External Loop Recorder 20% 7

5 9 Day S, et al. Am J Med. 1982; 73: 15-23.

 Short sampling window (approx. 12 sec)

Carotid Sinus Syndrome (CSS)

 8 studies, 2612 patients

 79% pts were without symptoms

Event Recorder Useful for infrequent events

Sra JS. Ann Intern Med. 1991;114:1013-1019

DG Benditt, UM Cardiac Arrhythmia Center

 Not a first line of testing

Patient Activator Reveal® Plus ILR 9790 Programmer

Linzer M. Am J Cardiol. 1990;66:214-219.

65 yo man with syncope

External loop recorder + -

Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

In Follow-up Diagnosed Undiagnosed Diagnosed Undiagnosed

Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

Diagnosed Undiagnosed Diagnosed Undiagnosed In follow-up

Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

 Limited utility in syncope evaluation

 Most useful in patients with structural heart

 Relatively ineffective for assessing

• Use the ILR to assess the correlation of rhythms captured

• Groups matched in age, sex, history of syncope, ECG, Echo

Moya A. Circulation. 2001; 104:1261-1267

History, physical exam, ECG, CSM, echo,