Syncope A Diagnostic and Treatment Strategy

1
SyncopeA Diagnostic and Treatment Strategy
Developed
by David G. Benditt, M.D. Richard
Sutton, DScMed University of Minnesota Medical
Center Royal Brompton Hospital, London,
UK
2
Presentation Overview

• Prevalence Impact
• Etiology
• Diagnosis Evaluation Options
• Specific Conditions
• Treatment Options
• Insights into more efficient and effective
  diagnosis and treatment of patients with syncope

3
Section IPrevalence and Impact
4
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.
5
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, Lher 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
199069160-175
6
Syncope Reported Frequency

• Individuals lt18 yrs
• Military Population 17- 46 yrs
• Individuals 40-59 yrs
• Individuals gt70 yrs

• 15
• 20-25
• 16-19
• 23

during a 10-year period
Brignole M, Alboni P, Benditt DG, et al. Eur
Heart J, 2001 22 1256-1306.
7
The Significance of Syncope

• 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. 199069160-175. 2 Silverstein
M, et al. JAMA. 19822481185-1189. 3 Martin G,
et al. Ann Emerg. Med. 198412499-504.
4 Kapoor W, et al. N Eng J Med.
1983309197-204. 5 National Disease and
Therapeutic Index, IMS America, Syncope and
Collapse 780.2 Jan 1997-Dec 1997. 6 Kapoor W,
et al. Am J Med. 198783700-708.
8
The Significance of Syncope

• Some causes of syncope are potentially fatal
• Cardiac causes of syncope have the highest
  mortality rates

1 Day SC, et al. Am J of Med 19827315-23. 2
Kapoor W. Medicine 199069160-175. 3 Silverstein
M, Sager D, Mulley A. JAMA. 19822481185-1189.
4 Martin G, Adams S, Martin H. Ann Emerg Med.
198413499-504.
9
Impact of Syncope
73 1
71 2
60 2
Proportion of Patients
37 2
Anxiety/Depression
Alter DailyActivities
RestrictedDriving
ChangeEmployment
1Linzer, J Clin Epidemiol, 1991. 2Linzer, J Gen
Int Med, 1994.
10
Section IIEtiology
11
Syncope A SymptomNot a Diagnosis

• Self-limited loss of consciousness and postural
  tone
• Relatively rapid onset
• Variable warning symptoms
• Spontaneous complete recovery

12
Causes of Syncope1
1Kapoor W. In Grubb B, Olshansky B (eds) Syncope
Mechanisms and Management. Armonk NY Futura
Publishing Co, Inc 1998 1-13.
13
Syncope Etiology
Orthostatic
Cardiac Arrhythmia
Structural Cardio- Pulmonary
Non- Cardio- vascular
Neurally- Mediated

• 1
• Vasovagal
• Carotid Sinus
• Situational
• Cough
• Post-
• micturition

• 2
• Drug
• Induced
• ANS
• Failure
• Primary
• Secondary

• 3
• Brady
• Sick sinus
• AV block
• Tachy
• VT
• SVT
• Long QT Syndrome

• 4
• Aortic Stenosis
• HOCM
• Pulmonary
• Hypertension

• 5
• Psychogenic
• Metabolic
• e.g. hyper-
• ventilation
• Neurological

24
11
14
4
12
Unknown Cause 34
DG Benditt, UM Cardiac Arrhythmia Center
14
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
15
Section IIIDiagnosis and Evaluation Options
16
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

17
Initial Evaluation(Clinic/Emergency Dept.)

• Detailed history
• Physical examination
• 12-lead ECG
• Echocardiogram (as available)

18
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...

19
Conventional Diagnostic Methods/Yield
9 Day S, et al. Am J Med. 1982 73 15-23. 10
Stetson P, et al. PACE. 1999 22 (part II) 782.
5 Kapoor, JAMA, 1992 6 Krahn, Circulation, 1995 7
Krahn, Cardiology Clinics, 1997. 8 Eagle K,, et
al. The Yale J Biol and Medicine. 1983 56 1-8.
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.
Structural Heart Disease MRI not studied
20
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

21
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)

22
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

23
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

24
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 1999912-948
25
Ambulatory ECG
26
Head-up Tilt Test (HUT)

• Unmasks VVS susceptibility
• Reproduces symptoms
• Patient learns VVS warning symptoms
• Physician is better able to give prognostic /
  treatment advice

27
Head-Up Tilt Test (HUT)
DG Benditt, UM Cardiac Arrhythmia Center
28
Electroencephalogram

• Not a first line of testing
• Syncope from Seizures
• Abnormal in the interval between two attacks
  Epilepsy
• Normal Syncope

29
Value of Event Recorder in Syncope
Asterisk denotes event marker
Linzer M. Am J Cardiol. 199066214-219.
30
Reveal Plus Insertable Loop Recorder
Patient Activator
Reveal Plus ILR
9790 Programmer
31
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
32
Randomized Assessment of Syncope Trial
Krahn A, Klein GJ, Skanes Y. Circulation 2001
10446-51.
33
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 lt 35
• Unable to give informed consent
• Major morbidity precluding one year of follow-up

Krahn A, Klein GJ, Skanes Y. Circulation 2001
10446-51.
34
RAST Results
Unexplained Syncope n60
In Follow-up n3
Diagnosed n14
Undiagnosed n13
Diagnosed n6
Undiagnosed n24
Krahn A, Klein GJ, Skanes Y. Circulation 2001
10446-51.
35
RAST Crossover Results
Unexplained Syncope n60
13/30 Undiagnosed after monitoring 6 accepted
crossover to conventional
24/30 Undiagnosed after conventional 21 accepted
crossover to ILR
Diagnosed n1
Undiagnosed n5
Diagnosed n8
Undiagnosed n5
In follow-up n8
Krahn A, Klein GJ, Skanes Y. Circulation 2001
10446-51.
36
RAST - Diagnoses
number of patients
Krahn A, Klein GJ, Skanes Y. Circulation 2001
10446-51.
37
Conventional EP Testing in Syncope

• Limited utility in syncope evaluation
• Most useful in patients with structural heart
  disease
• Heart disease..50-80
• No Heart disease18-50
• Relatively ineffective for assessing
  bradyarrhythmias

Brignole M, Alboni P, Benditt DG, et al. Eur
Heart Journal 2001 22 1256-1306.
38
EP Testing in SyncopeUseful Diagnostic
Observations

• Inducible monomorphic VT
• SNRT gt 3000 ms or CSRT gt 600 ms
• Inducible SVT with hypotension
• HV interval 100 ms (especially in absence of
  inducible VT)
• Pacing induced infra-nodal block

39
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 1041261-1267
40
ISSUE Study Design

• Multicenter, prospective

Moya A. Circulation. 2001 1041261-1267
41
ISSUE Study Results
Moya A. Circulation. 2001 1041261-1267
42
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

Moya A. Circulation. 2001 1041261-1267
43
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 1041261-1267
44
Symptom-Rhythm Correlation
Auto Activation Point
Patient Activation Point
45
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.
46
Unexplained Syncope Diagnosis
History and Physical Exam Surface ECG
ENT Evaluation
Endocrine Evaluation

• CV Syncope Workup
• Holter
• ELR or ILR
• Tilt Table
• Echo
• EPS

• Neurological Testing
• Head CT Scan
• Carotid Doppler
• MRI
• Skull Films
• Brain Scan
• EEG

• Other CV Testing
• Angiogram
• Exercise Test
• SAECG

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.
47
Typical Cardiovascular Diagnostic Pathway
Syncope
History and Physical, ECG
KnownSHD
NoSHD
gt 30 days gt 2 Events
lt 30 days
Echo
EPS
-

Treat
Tilt/ILR
Adapted from Linzer M, et al. Annals of Int Med,
1997. 12776-86. Syncope Mechanisms and
Management. Grubb B, Olshansky B (eds) Futura
Publishing 1999 Zimetbaum P, Josephson M. Annals
of Int Med, 1999. 130848-856. Krahn A et al. ACC
Current Journal Review,1999. Jan/Feb80-84.
48
Section IVSpecific Conditions
49
Neurally-Mediated Reflex Syncope (NMS)

• Vasovagal syncope (VVS)
• Carotid sinus syndrome (CSS)
• Situational syncope
• post-micturition
• cough
• swallow
• defecation
• blood drawing
• etc.

50
NM Reflex Syncope Pathophysiology

• Multiple triggers
• Variable contribution of vasodilatation and
  bradycardia

51
NMS Basic Pathophysiology
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
52
Vasovagal Syncope (VVS)Clinical Pathophysiology

• Neurally Mediated Physiologic Reflex Mechanism
  with two Components
• Cardioinhibitory ( HR )
• Vasodepressor ( BP )
• Both components are usually present

53
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

54
Spontaneous VVS
16.3
sec
Continuous Tracing
1 sec
DG Benditt, UM Cardiac Arrhythmia Center
55
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

56
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

57
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

58
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
• Reflex increase in efferent vagal activity and
  diminution of sympathetic tone results in
  bradycardia and vasodilation

Carotid Sinus
59
Carotid Sinus Hypersensitivity(CSH)

• Abnormal response to CSM
• Absence of symptoms attributable to CSS
• CSH reported frequent in fallers (Kenny)
• CSH ? CSS

60
CSS and Falls in the Elderly

• 30 of people gt65 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 gt50 yrs fallers presenting
  at ER 3

1Falling in the Elderly U.S. Prevalence Data.
Journal of the American Geriatric Society,
1995. 2 Campbell et al Age and Aging
198110264-270. 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
61
Section VTreatment Options
62
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)

63
Midodrine for Neurocardiogenic Syncope
Journal of Cardiovascular Electrophysiology Vol.
12, No. 8, Perez-Lugones, et al.
64
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.
65
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
102294-299. 2 Connolly S, et al. J Am Coll
Cardiol 1999 3316-20. 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.
66
VPS-IVasovagal 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 lt60/min if no isoproterenol
used, lt70/min if up to 2 mcg/min isoproterenol
used, or lt80/min if over 2 mcg/min isoproterenol
used
Connolly S, et al. J Am Coll Cardiol 1999 33
16-20.
67
VPS- I

• Endpoints
• Time to first syncope
• Outcome

2p 0.000022
Connolly S, et al. J Am Coll Cardiol 1999 33
16-20.
68
VPS- I
100
90
Control (No Pacemaker)
80
70
60
Cumulative Risk ()
50
2P0.000022
40
30
Pacemaker
20
10
0
15
12
9
6
3
0
Time in Months
NumberAt Risk
C 27 9 4 2 1 0 P 27 21 17 12 11 8
Connolly S, et al. J Am Coll Cardiol 1999 33
16-20.
69
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.
70
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
• gt 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 gt 40 years or drug refractory if lt 40 years

Sutton, R, et al. Circulation. 2000
102294-299.
71
VASIS

• Endpoints
• Time to first syncope

• Outcome

P 0.0006
Sutton, R, et al. Circulation. 2000
102294-299.
72
VASIS
Pacemaker
100
80
p0.0004
syncope-free
60
40
No-Pacemaker
20
0
2
3
4
5
6
Years
Sutton, R, et al. Circulation. 2000
102294-299.
73
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
102294-299.
74
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
• gt 55 yrs
• gt 3 syncopal episodes in 2 years
• HUT with relative bradycardia (trough HR lt60
  bpm)

Ammirati F, et al. Circulation. 2001 10452-57.
75
SYDIT

• Endpoints
• Time to first syncope
• Outcome

P0.004
Ammirati, et al. Circulation. 2001 10452-57.
76
SYDIT
Syncope-free Survival Intention-to-Treat
(n46/paced, 47/drug).
1.0
0.9
drug
pacemaker
P 0.0032
0.8
of syncope free pts
0.7
0.6
100
200
300
400
500
600
700
800
900
1000
0
Time (days)
Ammirati F, et al. Circulation. 2001 10452-57.
77
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 10452-57.
78
VPS-II Phase IVasovagal 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
• gt 6 syncope events ever or gt 3 syncope events in
  2 years or gt 1 syncope event in 6 months and,
• Positive HUT with syncope or presyncope and a
  heart rate blood pressure product lt9000

Presented at the 23rd Annual Scientific Sessions
of the North American Society of Pacing and
Electrophysiology. Late Breaking Clinical Trials,
May 11, 2002.
79
VPS-II Phase I

• Endpoints
• Time to first syncope
• Outcome

P0.153
Presented at the 23rd Annual Scientific Sessions
of the North American Society of Pacing and
Electrophysiology. Late Breaking Clinical Trials,
May 11, 2002.
80
VPS-II Phase I
0.4
0.3
ODO
DDD
Cumulative Risk of Syncope
0.2
P 0.153 (one-sided)
0.1
0.0
0
1
2
3
4
5
6
ODO 40 37 35 32 31 21 DDD 39 36 34 33 33 17
Number at Risk
Presented at the 23rd Annual Scientific Sessions
of the North American Society of Pacing and
Electrophysiology. Late Breaking Clinical Trials,
May 11, 2002.
81
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.
82
VVS Pacing Trials Conclusions

• DDD pacing reduces the risk of syncope
• in patients with recurrent, refractory,
• highly-symptomatic, cardioinhibitory
• vasovagal syncope.

83
SAFE PACE Study Design

• Randomized controlled trial (N175)
• 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 381491-1496.
84
SAFE PACE Inclusion Criteria

• Consecutive adults attending accident and
  emergency department
• gt 50 Years
• - Experienced non-accidental fall
• Positive response to CSM

Kenny RA, J Am Coll Cardiol 2001 381491-1496.
85
SAFE PACE Screening Process
Accident and Emergency Attendees gt 50 Yrs
Falls or Syncope
Non-accidental Fall
CSM Performed
Cardioinhibitory or Mixed CSH
RCT
Control
Pacemaker
Kenny RA, J Am Coll Cardiol 2001 381491-1496.
86
SAFE PACE Screening Results
RCT (n175)

• No pacing intervention

• Medtronic Thera DR(Rate Drop ResponseAlgorithm)

Kenny RA, J Am Coll Cardiol 2001 381491-1496.
87
SAFE PACE ResultsNumber of Falls
70ReductionOR 0.42 95CI 0.23, 0.75
Falls during 12 months post randomization
Crude adjustment calculation
Kenny RA, J Am Coll Cardiol 2001 381491-1496.
88
SAFE PACE ResultsNumber of Syncopal Episodes
50ReductionOR 0.53 95 CI 0.23 1.20 ns
Syncopal events 12 months past
randomization Crude adjustment calculation
Kenny RA, J Am Coll Cardiol 2001 38000-000.
89
SAFE PACE ResultsNumber of Injury Events
70Reduction
Injurious events 12 months post randomization
Kenny RA, J Am Coll Cardiol 2001 381491-1496.
90
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 381491-1496.
91
Role of Pacing in CSS --Syncope Recurrence Rate

• Class I indication for pacing (AHA and BPEG)
• Limit pacing to CSS that is
• Cardioinhibitory
• Mixed
• DDD/DDI superior to VVI

57
Recurrence
6
(Mean follow-up 6 months)
Brignole et. Al. Diagnosis, natural history and
treatment. Eur JCPE. 1992 4247-254
92
Section VIInsights into More Efficient and
Effective Diagnosis and Treatment
93
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

94
Syncope Due to Arrhythmia or Structural CV
DiseaseGeneral 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

95
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

96
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

97
Rhythms During Recurrent Syncope
Bradycardia 36
Normal Sinus Rhythm 58
Normal Sinus Rhythm 58
Tachyarrhythmia 6
Krahn A, et al. Circulation. 1999 99 406-410
98
AECG 74 yr Male, Syncope
From the files of DG Benditt, UM Cardiac
Arrhythmia Center
99
Syncope Torsades
From the files of DG Benditt, UM Cardiac
Arrhythmia Center
100
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.
101
Infra-His Block
From the files of DG Benditt, UM Cardiac
Arrhythmia Center
102
Drug-Induced QT Prolongation

• Antiarrhythmics
• Class IA ...Quinidine, Procainamide, Disopyramide
• Class IIISotalol, Ibutilide, Dofetilide,
  Amiodarone, (NAPA)
• Antianginal Agents
• (Bepridil)
• Psychoactive Agents
• Phenothiazines, Amitriptyline, Imipramine,
  Ziprasidone
• Antibiotics
• Erythromycin, Pentamidine, Fluconazole
• Nonsedating antihistamines
• (Terfenadine), Astemizole
• Others
• (Cisapride), Droperidol

103
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

104
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

105
Conclusion

• Syncope is a common symptom,
• often with dramatic consequences,
• which deserves thorough investigation
• and appropriate treatment of its cause.

106
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 patients
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.
107
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 M
edtronic.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.
108
Additional Slides
109
Falls -- Incidence, Recurrence, CHS
50 1
30 1
Percent of People
23 2
Incidencegt 65 yrs. old
Recurrence
CSH presentin fallers gt 50 yrs.presenting at ER
1 Falling in the Elderly, 1995. 2 Richardson,
PACE, 1997.
Carotid Sinus Hypersensitivity
110
VVS Pacing TrialsComparison Summary
111
Pacing in VVS

• Two randomized, controlled trials suggest
  benefit in selected patients with multiple (gt5
  lifetime) syncope recurrences and one or more of
  
• prominent cardioinhibitory features
• asystolic pause gt10 seconds
• sustained HRlt40/minute

112
VVS Recurrences

• 35 of patients report syncope recurrence during
  follow-up 3 years
• Positive HUT with gt6 lifetime syncope episodes
  recurrence risk gt50 over 2 years

Sheldon et al. Circulation 1996 93
973-81. Savage et al. STROKE 1985 16 626-29.
113
SAFE PACE 2 Syncope and Falls in the Elderly

• 30 of individuals gt65 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 gt80 yrs

Kenny RA, J Am Coll Cardiol 2001 381491-1496.
114
Rate Drop Response Overview
Detection Options
Both
Drop Detect
Low Rate Detect
Detection occurs when either Drop Detection or
Low Rate Detection criteria are met
Detects relative heart rate drops of a
pre-determined size
Detects heart rate that falls to a user-defined
lower rate
Rate Drop Detection in Medtronic Kappa Series
Pacemakers
115
Drop Detection with Intervention
Drop Detection Method Drop Size 25, Drop Rate 70
110
Peak Rate90 bpm
100
90
80
Drop Size25 bpm
Ventricular Rate
Drop Rate
70
60
2 consecutive beats
lt
Drop
50
Size and Drop Rate
40
Rate Drop Detection in Medtronic Kappa Series
Pacemakers
116
Drop Detect Peak Rate
Drop Detection Method Drop Size 25
120
Peak Rate90 bpm
110
100
90
Ventricular Rate
80
Drop Size25
bpm
70
60
50
40
Rate Drop Detection in Medtronic Kappa Series
Pacemakers
117
Low Rate Detect
Low Rate Detection Method Lower Rate 40,
Detection beats 2
110
100
90
80
Ventricular Rate
70
2 consecutive paced
60
beats at Lower Rate
50
40
Lower Rate
30
Rate Drop Detection in Medtronic Kappa Series
Pacemakers
118
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
119
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
120
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

121
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

60 - 80
DG Benditt, Tilt Table Testing, 1996.
122
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

123
Tilt-Training Clinical Outcomes

• 42 HUT positive (2113 min) VVS patients
• Home training two 30 minute sessions daily
• Outcomes
• 41/42 pts ---gt45 min asymptomatic HUT
• Clinical follow-up 15.17.8 mos
• 36 pts syncope free
• 4 pts presyncope
• 1 pt syncope recurrences

Reybrouck et al. PACE 2000 23493-8