Transcript Syncope A Diagnostic and Treatment Strategy

Syncope
A Diagnostic and
Treatment Strategy
Developed by:
David G. Benditt, M.D.
Richard Sutton, DScMed
University of Minnesota Medical Center
Royal Brompton Hospital, London, UK
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.
The Significance of Syncope
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*
Brignole M, Alboni P, Benditt DG, et al. Eur Heart J, 2001; 22: 1256-1306.
23%
*during a 10-year period
The Significance of Syncope
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
1
Kapoor W, Med. 1990;69:160-175.
2 Silverstein M, et al. JAMA. 1982;248:1185-1189.
4 Kapoor W, et al. N Eng J Med. 1983;309:197-204.
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.
The Significance of Syncope
 Some causes of syncope are potentially fatal
 Cardiac causes of syncope have the highest mortality
rates
Syncope Mortality
25%
20%
15%
10%
5%
0%
Overall
1
Day SC, et al. Am J of Med 1982;73:15-23.
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.
2
Due to Cardiac Causes
Impact of Syncope
100%
80%
73% 1
71% 2
60% 2
60%
37% 2
40%
20%
0%
1Linzer,
2Linzer,
Anxiety/
Depression
J Clin Epidemiol, 1991.
J Gen Int Med, 1994.
Alter Daily
Activities
Restricted
Driving
Change
Employment
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
Causes of Syncope1
Prevalence
(Mean) %
Prevalence
(Range) %
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
Cause
Reflex-mediated:
1Kapoor
W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc:
1998; 1-13.
Syncope: Etiology
NeurallyMediated
1
• Vasovagal
• Carotid
Sinus
• Situational
Cough
Postmicturition
24%
Orthostatic
2
3
• Brady
• Drug
Induced
• ANS
Failure
Sick sinus
AV block
Primary
Secondary
11%
Cardiac
Arrhythmia
• Tachy
VT*
SVT
Structural
CardioPulmonary
4
• Aortic
Stenosis
• HOCM
• Pulmonary
Hypertension
5
• Psychogenic
• Metabolic
e.g. hyperventilation
• Neurological
4%
12%
• Long QT
Syndrome
14%
Unknown Cause = 34%
DG Benditt, UM Cardiac Arrhythmia Center
NonCardiovascular
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%

External Loop Recorder
20% 7
7
(2-3 weeks duration)

Insertable Loop Recorder
65-88% 6, 7
(up to 14 months duration)
Neurological †
(Head CT Scan, Carotid Doppler)
1
Kapoor, et al N Eng J Med, 1983.
2 Kapoor, Am J Med, 1991.
3 Linzer, et al. Ann Int. Med, 1997.
4 Kapoor, Medicine, 1990.
0-4%
4,5,8,9,10
9 Day S, et al. Am J Med. 1982; 73: 15-23.
Kapoor, JAMA, 1992
10 Stetson P, et al. PACE. 1999; 22 (part II): 782.
Krahn, Circulation, 1995
7 Krahn, Cardiology Clinics, 1997.
8 Eagle K,, et al. The Yale J Biol and Medicine. 1983; 56: 1-8.
5
6
*
†
Structural Heart Disease
MRI not studied
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 AECG
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
Holter (24-48 hours)
Comments
Useful for infrequent events
Event Recorder
Useful for infrequent events
Loop Recorder
Limited value in sudden LOC
Useful for infrequent events
Implantable type more
convenient (ILR)
Wireless (internet)
Event Monitoring
In development
Head-up Tilt Test (HUT)
 Unmasks VVS
susceptibility
 Reproduces symptoms
 Patient learns VVS
warning symptoms
 Physician is better able
to give prognostic /
treatment advice
Head-Up Tilt Test (HUT)
DG Benditt, UM Cardiac Arrhythmia Center
Electroencephalogram
 Not a first line of testing
 Syncope from Seizures
 Abnormal in the interval
between two attacks – Epilepsy
 Normal – Syncope
Value of
Event
Recorder
in
Syncope
*Asterisk denotes
event marker
Linzer M. Am J Cardiol. 1990;66:214-219.
®
Reveal Plus
Insertable Loop Recorder
Patient Activator
Reveal® Plus ILR
9790 Programmer
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
Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.
+
ILR
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
Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.
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
Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.
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
Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.
RAST - Diagnoses
14
number of patients
12
10
ILR
Conventional
8
6
4
2
0
Bradycardia
Tachycardia
Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.
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 tiltnegative (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
Moya A. Circulation. 2001; 104:1261-1267
ISSUE Study Results
Results
Recurrent Event Occurrence (#)
Mean Time to Recurrent Event
Tilt-Negative
Syncope (Isolated)
Tilt-Positive
Syncope
n=82
n=29
34% (28)
34% (10)
105 days (47-226)
59 (22-98)
29% (24)
28% (8)
(range)
ILR ECG Documented (#)
Tachyarrhythmia
Bradycardia
2% (2)
16% (13)
21% (6)
–Sinus Brady
2% (2)
3% (1)
–Sinus Arrest
12% (10)
17% (5)
–AV Block
Total Arrhythmic
Normal Sinus Rhythm
Moya A. Circulation. 2001; 104:1261-1267
1% (1)
18% (15)
21% (6)
11% (9)
7% (2)
ISSUE Study
 Conclusions:
• Homogeneous findings from tilt-negative and tiltpositive 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
Moya A. Circulation. 2001; 104:1261-1267
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
Moya A. Circulation. 2001; 104:1261-1267
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
Neurological
Testing
CV Syncope
Workup
• Holter
• Head CT Scan
• ELR or ILR
• Carotid Doppler
• Tilt Table
• MRI
• Echo
• Skull Films
• EPS
Endocrine
Evaluation
Other CV
Testing
• Angiogram
• Exercise Test
• SAECG
• 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
SHD
No
SHD
> 30 days;
> 2 Events
Echo
< 30 days
EPS
Tilt/ILR
+
Treat
Tilt
ILR
Tilt
Holter/ ELR
ILR
Adapted from:
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
Cerebral
Cortex
Feedback via
Carotid Baroreceptors
Other Mechanoreceptors
Baroreceptors
Parasympathetic (+)
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
DG Benditt, UM Cardiac Arrhythmia Center
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…

1Falling
CSH present in 23% of >50 yrs fallers presenting at ER 3
in the Elderly: U.S. Prevalence Data. Journal of the American Geriatric Society, 1995.
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
2
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)
Symptom – Free Interval
Midodrine for Neurocardiogenic Syncope
100
80
60
Midodrine
Fluid
40
20
p < 0.001
0
0
20
40
60
80
Months
Journal of Cardiovascular Electrophysiology Vol. 12, No. 8, Perez-Lugones, et al.
100
120
140
160
180
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
1325-1335.
G, et al. ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmic Devices. Circulation. 1998; 97:
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
2
R, et al. Circulation. 2000; 102:294-299.
Connolly S, et al. J Am Coll Cardiol 1999; 33:16-20.
3 Ammirati
4
F, et al. Circulation. 2002; 104: 52-57.
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*
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.
*a trough heart rate <60/min if no isoproterenol used,
<70/min if up to 2 mcg/min isoproterenol used, or <80/min
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
Control
(No Pacemaker)
80
70
60
Cumulative
Risk
50
(%)
40
2P=0.000022
30
Pacemaker
20
10
0
0
Number
At Risk
C 27
P 27
3
9
21
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.
6
9
Time in Months
12
15
4
17
1
11
0
8
2
12
VPS-I
 Conclusion:
Dual-chamber pacing with rate drop response
reduces the likelihood of syncope in patients
with recurrent VVS.
Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.
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
 Patient Inclusion Criteria:
 > 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:
RESULTS
Number of patients w/syncopal recurrence
Median time to first recurrence (months)*
*P= 0.0006
Sutton, R, et al. Circulation. 2000; 102:294-299.
Pacemaker
No
Pacemaker
(n= 19)
(n=23)
1 (5%)
14 (61%)
15
5
VASIS
Pacemaker
% syncope-free
100
80
p=0.0004
60
40
No-Pacemaker
20
0
# of
pts 40
31
Sutton, R, et al. Circulation. 2000; 102:294-299.
2
23
3
Years
4
5
6
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.
Sutton, R, et al. Circulation. 2000; 102:294-299.
SYDIT
Syncope Diagnosis and Treatment Study
 Study Design:
93 patients randomized, prospective, multicenter
_
46 DDD pacemaker with rate drop response (RDR)
_
47 Atenolol 100 MG/D
 Patient Inclusion Criteria:
 > 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%)
390
135
Median time to first recurrence (days)
*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
% of syncope free pts
0.9
drug
pacemaker
P = 0.0032
0.8
0.7
0.6
0
100
200
300
400
500
600
Time (days)
Ammirati F, et al. Circulation. 2001; 104:52-57.
700
800
900
1000
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.
Ammirati F, et al. Circulation. 2001; 104:52-57.
VPS-II: Phase I
Vasovagal Pacemaker Study-II
 Study Design:
100 patients, randomized, prospective, multicenter
_
50 DDD pacemaker with rate drop response (RDR)
_
50 ODO pacemaker (inactive mode)
 Patient Inclusion Criteria:
> 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)
Number of patients w/syncopal recurrence
16 (32%)
22 (44%)
28.7%
-
Relative Risk Reduction*
*P=0.153
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
0.4
Cumulative Risk of
Syncope
0.3
ODO
DDD
0.2
P = 0.153 (one-sided)
0.1
0.0
0
Number at Risk
1
ODO
DDD
40
39
2
37
36
3
35
34
4
32
33
5
31
33
6
21
17
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
 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.
Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking
Clinical Trials, May 11, 2002.
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
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
SAFE PACE Screening Process
Accident and Emergency Attendees > 50 Yrs
Falls or Syncope
Non-accidental Fall
CSM Performed
Cardioinhibitory or Mixed CSH
RCT
Control
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
Pacemaker
SAFE PACE Screening Results
RCT (n=175)
Control
(n=88)
• No pacing intervention
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
Pacemaker
(n=87)
• Medtronic Thera DR
(Rate Drop Response
Algorithm)
SAFE PACE Results
Number of Falls
% Participants
w/Falls
Control
Pacemaker
n=87
n=84
60%
58%
Total Number of
Falls*
699
Mean Number of
Falls**
9.3
* Falls during 12 months post randomization
** Crude adjustment calculation
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
216
4.1
70%
Reduction
[OR 0.42; 95%
CI: 0.23, 0.75]
SAFE PACE Results
Number of Syncopal Episodes
% Participants
w/Syncopal Events
Total Number of
Syncopal Events
Mean Number Syncopal
Events
Control
Pacemaker
N=87
N=84
22%
11%
47
22
1.14
* Syncopal events 12 months past randomization
** Crude adjustment calculation
Kenny RA, J Am Coll Cardiol 2001; 38:000-000.
0.20
50%
Reduction
[OR 0.53; 95%
CI 0.23; 1.20 ns]
SAFE PACE Results
Number of Injury Events
Control
Pacemaker
n= 87
n= 84
% Participants w/Injurious
Events
41%
35%
Total Number Injury
Events
202
61
4
3
198
58
-Fractures
-Soft Tissue Injury
* Injurious events 12 months post randomization
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
70%
Reduction
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%
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
Role of Pacing in CSS -Syncope Recurrence Rate
Class I indication for
pacing (AHA and BPEG)
Limit pacing to CSS that
is:
•Cardioinhibitory
•Mixed
75%
57%
50%
25%
DDD/DDI superior to VVI
%6
(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
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
AECG: 74 yr Male, Syncope
From the files of DG Benditt, UM Cardiac Arrhythmia Center
Syncope: Torsades
From the files of DG Benditt, UM Cardiac Arrhythmia Center
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
From the files of DG Benditt, UM Cardiac Arrhythmia Center
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 dualchamber 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 (longQT/Brugada)
 Drug therapy may be an alternative in many
cases
Conclusion
Syncope is a common symptom,
often with dramatic consequences,
which deserves thorough investigation
and appropriate treatment of its cause.
Disclaimer
INDICATIONS
9526 Reveal® Plus Insertable Loop Recorder
The Reveal Plus Insertable Loop Recorder (ILR) is an implantable patient activated monitoring system that records subcutaneous
ECG and is indicated for patients who experience transient symptoms that may suggest a cardiac arrhythmia.
9790 Programmer
The Medtronic 9790 Programmers are portable, microprocessor based instruments used to program Medtronic implantable
devices.
6191 Activator
The Model 6191 Activator is intended for use in combination with a Medtronic Model 9525 Reveal ® and the Model 9526 Reveal
Plus Insertable Loop Recorders.
CONTRAINDICATIONS
There are no known contraindications for the implantation of the Reveal Plus ILR. However, the patient’s particular medical
condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated.
WARNINGS/PRECAUTIONS
9526 Reveal Plus Insertable Loop Recorder
Patients with the Reveal Plus ILR should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation,
electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation to avoid electrical reset of the device, and/or
inappropriate sensing.
6191 Activator
Operation of the Model 6191 Activator near sources of electromagnetic interference, such as cellular phones, computer monitors,
etc., may adversely affect the performance of this device.
See the appropriate technical manual for detailed information regarding indications, contraindications, warnings, and
precautions.
Caution: Federal law (U.S.A.) restricts this device to sale by or on the order of a physician.
Disclaimer
INDICATIONS
Medtronic.Kappa 700 Series Pacemakers
The Medtronic.Kappa 700 Series pacemakers are indicated for rate adaptive pacing in patients who may benefit from increased pacing rates
concurrent with increases in activity and are also indicated for dual chamber and atrial tracking modes in patients who may benefit from
maintenance of AV synchrony. Dual chamber modes are specifically indicated for treatment of conduction disorders that require restoration of
both rate and AV synchrony, which include various degrees of AV block to maintain the atrial contribution to cardiac output and VVI
intolerance (e.g., pacemaker syndrome) in the presence of persistent sinus rhythm.
9790 Programmer
The Medtronic 9790 Programmers are portable, microprocessor based instruments used to program Medtronic implantable devices.
9462
The Model 9462 Remote Assistant is intended for use in combination with a Medtronic implantable pacemaker with Remote Assistant
diagnostic capabilities.
CONTRAINDICATIONS
The Medtronic.Kappa 700 Series pacemakers are contraindicated for the following applications:
· Dual chamber atrial pacing in patients with chronic refractory atrial tachyarrhythmias.
· Asynchronous pacing in the presence (or likelihood) of competitive paced and intrinsic rhythms.
· Unipolar pacing for patients with an implanted cardioverter-defibrillator (ICD) because it may cause unwanted delivery or inhibition of ICD
therapy.
WARNINGS/PRECAUTIONS
Medtronic.Kappa 700 Series patients should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation,
electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation to avoid electrical reset of the device, inappropriate
sensing and/or therapy.
See the appropriate technical manual for detailed information regarding indications, contraindications, warnings, and precautions.
Caution: Federal law (U.S.A.) restricts this device to sale by or on the order of a physician.
Additional Slides
Falls -- Incidence, Recurrence, CHS*
75%
50% 1
50%
30% 1
23% 2
25%
0%
Incidence
> 65 yrs. old
Recurrence
CSH* present
in fallers > 50 yrs.
presenting at ER
1 Falling
2
in the Elderly, 1995.
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
Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.
Rate Drop Response Overview
Detection Options
Drop
Detect
Detects relative
heart rate drops
of a predetermined size
Both
Detection occurs
when either Drop
Detection or Low
Rate Detection
criteria are met
Rate Drop Detection in Medtronic Kappa® Series Pacemakers
Low Rate
Detect
Detects heart
rate that falls to
a user-defined
lower rate
Drop Detection with Intervention
Drop Detection Method: Drop Size 25, Drop Rate 70
110
100
Peak Rate=90 bpm
Ventricular Rate
90
80
70
Drop Size=25 bpm
Drop Rate
60
50
40
Rate Drop Detection in Medtronic Kappa® Series Pacemakers
2 consecutive beats < Drop
Size and Drop Rate
Drop Detect Peak Rate
Drop Detection Method: Drop Size 25
120
Ventricular Rate
110
Peak Rate=90 bpm
100
90
80
70
60
50
40
Rate Drop Detection in Medtronic Kappa® Series Pacemakers
Drop Size=25
bpm
Low Rate Detect
Low Rate Detection Method: Lower Rate 40, Detection beats 2
110
100
Ventricular Rate
90
80
70
60
2 consecutive paced
beats at Lower Rate
50
40
Lower Rate
30
Rate Drop Detection in Medtronic Kappa® Series Pacemakers
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 Detection in Medtronic Kappa® Series Pacemakers
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
Rate Drop Detection in Medtronic Kappa® Series Pacemakers
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
 Supine and upright
 Tilt to 60-80 degrees
 Isoproterenol
 Re-tilt
DG Benditt, Tilt Table Testing, 1996.
60° - 80°
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