Syncope

Syncope
A Diagnostic and
Treatment Strategy
David G. Benditt, M.D. Richard Sutton, DScMed

University of Minnesota Medical School Royal Brompton Hospital
Minneapolis, MN USA London, UK
Transient Loss of Consciousness (TLOC)
Classification of Transient Loss of Consciousness (TLOC)
Real or Apparent TLOC
Syncope Disorders Mimicking Syncope

• Neurally-mediated reflex • With loss of consciousness, i.e.,
syndromes seizure disorders, concussion
• Orthostatic hypotension • Without loss of consciousness,
i.e., psychogenic “pseudo-
• Cardiac arrhythmias syncope”
• Structural cardiovascular
disease
Brignole M, et al. Europace, 2004;6:467-537.

Syncope – A Symptom, Not a Diagnosis
 Self-limited loss of consciousness and postural tone

 Relatively rapid onset
 Variable warning symptoms
 Spontaneous, complete, and usually prompt recovery without
medical or surgical intervention
Underlying
Underlying mechanism
mechanism isis
transient
transient global
global cerebral
cerebral hypoperfusion.
hypoperfusion.

Presentation Overview
I. Etiology, Prevalence, Impact

II. Diagnosis
III. Specific Conditions and Treatment
IV. Special Issues
Section I:
Etiology, Prevalence, Impact
Causes of True Syncope
Structural
Structural
Neurally-
Neurally- Cardiac
Cardiac
Orthostatic
Orthostatic Cardio-
Cardio-
Mediated
Mediated Arrhythmia
Arrhythmia Pulmonary
Pulmonary
1 2 3 4
• VVS • Drug-Induced • Brady • Acute
• CSS • ANS Failure SN Myocardial
Dysfunction Ischemia
• Situational Primary
AV Block • Aortic
Cough Secondary
• Tachy Stenosis
Post-
VT • HCM
Micturition
SVT • Pulmonary
• Long QT Hypertension
Syndrome • Aortic
Dissection
Unexplained Causes = Approximately 1/3

DG Benditt, MD. U of M Cardiac Arrhythmia Center
Syncope Mimics
 Acute intoxication (e.g., alcohol)

 Seizures
 Sleep disorders
 Somatization disorder (psychogenic pseudo-syncope)
 Trauma/concussion
 Hypoglycemia
 Hyperventilation

Impact of Syncope
 40% will experience syncope

at least once in a lifetime1
 1-6% of hospital admissions2
 1% of emergency room visits
per year3,4
 10% of falls by elderly are due
to syncope5
 Major morbidity reported in 6%1
eg, fractures, motor vehicle accidents
 Minor injury in 29%1

eg, lacerations, bruises
1
Kenny RA, Kapoor WN. In: Benditt D, et al. eds. The Evaluation and 3
Brignole M, et al. Europace. 2003;5:293-298.
Treatment of Syncope. Futura;2003:23-27. 4
Blanc J-J, et al. Eur Heart J. 2002;23:815-820.
2
Kapoor W. Medicine. 1990;69:160-175. 5
Campbell A, et al. Age and Ageing. 1981;10:264-270.
Impact of Syncope: US Trends
Inpatient Trend* Physician Office Visits**

(000s) (000s)
*All patients discharged with syncope and collapse **Syncope and collapse (ICD-9 Code: 780.2)
(ICD-9 Code:780.2) listed among diagnoses. listed as primary reason for visit.
NHDS 2003. NAMCS 2002.
Impact of Syncope: US Trends
Emergency Hospital
Department Visits* Outpatient Visits*
(000s) (000s)
*Syncope and collapse (ICD-9 Code:780.2) listed as + Not available

primary reason for visit.
NHAMCS 2002.
Impact of Syncope:
NHS Hospitals, England, 2002-2003*
 74,813 hospital consults for

syncope and collapse
 80% required hospital admission
 Average length of stay: 6.1 days
 327,201 hospital bed days,
second only to senility
*Hospital Episode Statistics, Dept. of Health, Eng. 2002-2003.

Impact of Syncope: Costs
 Estimated hospital costs exceeded $10 billion US1

 Estimated physician office expenses exceeded $470 million2
 £104,285 spent on 1,334 patients with syncopal codes (UK)
(EaSyAS)3
• Hospital admission: 67% of investigational costs
 Over $7 billion is spent annually in the US
to treat falls in older adults4
1
Kenny RA, Kapoor WN. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:23-27.
2
OutPatientView v. 6.0. Solucient LLC, Evanston IL.
3
Farwell D, et al. J Cardiovasc Electrophysiol. 2002;13(Supp):S9-S13.
4
Olshansky B. In: Grubb B and Olshansky B. eds. Syncope: Mechanisms and Management. Futura. 1998:15-71.
Impact of Syncope: Quality of Life
73%1 71%2
Percent of Patients
60%2
37%2
Anxiety/ Alter Daily Restricted Change

Depression Activities Driving Employment
Linzer M. J Clin Epidemiol. 1991;44:1037.

1
Linzer M. J Gen Int Med. 1994;9:181.

2
Quality of Life:
UK Population Norms vs. Syncope Patients
49%
43%
37% 36%
% Prevalence
26%
19%
9%
3% 4%
1%
Mobility Usual Self-Care Pain/ Anxiety/

Activities Discomfort Depression
Rose M, et al. J Clin Epidemiol. 2000;53:1209-1216.

Syncope Mortality
 Low mortality vs.

high mortality
 Neurally-mediated
syncope vs. syncope
with a cardiac cause
Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope.
N Engl J Med. 2002;347(12):878-885. [Framingham Study Population]
Implications of Syncope for Driving a Vehicle
 Those who drive and have  If the patient has sufficient

recurrent syncope risk their warning of impending syncope
lives and the lives of others – Driving may be permitted
 Places considerable burden
on the physician
 Essentialto know local laws
and physician responsibilities
 Some states – Invasion of
privacy to notify motor
vehicle department*
• Other states – Reporting
is mandatory*
Olshansky B, Grubb B. In: Syncope: Mechanisms and Management. Futura. Armonk, NY. 1998.
*Medtronic, Inc. Follow-up Forum. 1995/96;1(3):8-10.
Challenges of Syncope
 Diagnosis
• Complex
 Quality of life implications
• Work
• Mobility (automobiles)
• Psychological
 Cost
• Cost/year
• Cost/diagnosis
Section II:
Diagnosis
Diagnostic Objectives
 Distinguish true syncope from syncope mimics

 Determine presence of heart disease
 Establish the cause of syncope with
sufficient certainty to:
• Assess prognosis confidently
• Initiate effective preventive treatment
A Diagnostic Plan is Essential
 Initial Examination
• Detailed patient history
• Physical exam
• ECG
• Supine and upright
blood pressure
 Monitoring
• Holter
• Event
• Insertable Loop Recorder (ILR)
 Cardiac Imaging
 Special Investigations
• Head-up tilt test
• Hemodynamics
• Electrophysiology study
Diagnostic Flow Diagram for TLOC
Initial Evaluation
Syncope Not Syncope
Certain Suspected Unexplained

Diagnosis Diagnosis Syncope
Cardiac Neurally-Mediated or Frequent or Severe Single/Rare Confirm with

Likely Orthostatic Likely Episodes Episodes Specific Test or
Specialist
Consultation
Cardiac Tests for Neurally- Tests for Neurally- No Further

Tests Mediated Syncope Mediated Syncope Evaluation
+ - + - + -
Re-Appraisal Re-Appraisal
Treatment Treatment Treatment Treatment

Initial Exam: Detailed Patient History
 Circumstances of recent event

• Eyewitness account of event
• Symptoms at onset of event
• Sequelae
• Medications
 Circumstances of more
remote events
 Concomitant disease,
especially cardiac
 Pertinent family history
• Cardiac disease
• Sudden death
• Metabolic disorders
 Past medical history
• Neurological history
• Syncope
Initial Exam: Thorough Physical
 Vital signs
• Heart rate
• Orthostatic blood pressure change
 Cardiovascular exam: Is heart disease present?
• ECG: Long QT, pre-excitation, conduction system disease
• Echo: LV function, valve status, HCM
 Neurological exam
 Carotid sinus massage
• Perform under clinically appropriate conditions preferably
during head-up tilt test
• Monitor both ECG and BP
Carotid Sinus Massage (CSM)
 Method1  Absolute contraindications2

• Massage, 5-10 seconds • Carotid bruit, known significant
carotid arterial disease,
• Don’t occlude previous CVA, MI last 3 months
• Supine and upright posture
(on tilt table)  Complications
 Outcome • Primarily neurological
• 3 second asystole and/or • Less than 0.2%3
50 mmHg fall in systolic BP
with reproduction of symptoms • Usually transient
= Carotid Sinus Syndrome
1
Kenny RA. Heart. 2000;83:564.
2
Linzer M. Ann Intern Med. 1997;126:989.
3
Munro N, et al. J Am Geriatr Soc. 1994;42:1248-1251.
Other Diagnostic Tests
 Ambulatory ECG
• Holter monitoring
• Event recorder
− Intermittent vs. Loop
− Insertable Loop Recorder (ILR)
 Head-Up Tilt (HUT)

• Includes drug provocation (NTG, isoproterenol)
• Carotid Sinus Massage (CSM)
 Adenosine Triphosphate Test (ATP)
 Electrophysiology Study (EPS)

Heart Monitoring Options
OPTION
12-Lead 10 Seconds
2 Days
Holter Monitor
Event Recorders 7-30 Days

(non-lead and loop)
Up to 14
ILR Months
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
TIME (Months)

Diagnostic Assessment: Yields
(N=3411 to 4332)
Yield (%)
Initial Evaluation
History, Physical Exam, ECG, Cardiac Massage

38-40
Other Tests/Procedures
Head-Up Tilt 27
External Cardiac Monitoring 5-13
Insertable Loop Recorder (ILR) 43-883-5
EP Study <2-5
Exercise Test 0.5
EEG 0.3-0.5
No data
MRI
available6
References Available
Neurological Tests:
Rarely Diagnostic for Syncope
 EEG, Head CT, Head MRI

 May help diagnose seizure

Head-Up Tilt Test (HUT)
 Protocols vary
 Useful as diagnostic adjunct
in atypical syncope cases
60° - 80°
 Useful in teaching patients
to recognize prodromal
symptoms
 Not useful in assessing
treatment

Head-up Tilt Test
Click once on image to play video.
Carlos Morillo, MD, FRCPC

Professor, Faculty of Health Sciences
McMaster University, Hamilton Ontario
Head-Up Tilt Test:
ECG Leads and Intra-Arterial Pressure Tracing
DG Benditt, MD. U of M Cardiac Arrhythmia Center

Adenosine Triphosphate (ATP) Test
 Ongoing investigation  Seems to identify a unique

in the US mechanism of syncope found
in patients with:
 Provokes a short and
potent cardioinhibitory • Advanced age
vasovagal response • More hypertension
 Advantages • More ECG abnormalities
• Simple
• Inexpensive
• Correlation with
pacing benefit
Brignole M. Heart. 2000;83:24-28.

Donateo P. J Am Coll Cardiol. 2003;41:93-98.
Flammang D. Circ. 1999;99:2427-2433.
Insertable Loop Recorder (ILR)
Click once on black screen to play video.
Reveal® Plus ILR Typical Location of the

Reveal® Plus ILR
The ILR is an implantable patient – and automatically – activated

monitoring system that records subcutaneous ECG and is
indicated for:
 Patients with clinical syndromes or situations at increased risk of
cardiac arrhythmias
 Patients who experience transient symptoms that may suggest a
cardiac arrhythmia
Click once on black screen to play video.

Symptom-Rhythm Correlation with the ILR
CASE: 56 year-old woman with CASE: 65 year-old man with

refractory syncope accompanied syncope accompanied by brief
with seizures. retrograde amnesia.
Medtronic data on file.

Randomized Assessment of Syncope Trial (RAST)
60 Patients
Unexplained Syncope
EF > 35%
30 Patients 30 Patients
Primary Conventional
ILR Testing
Strategy 14 6 (AECG, Tilt, EPS)
++ ++
Diagnosis
– –
1 8
++ ++
Crossover AECG, Tilt, ILR
EP Study
Results:
 Combining primary strategy with crossover, the diagnostic yield is
43% ILR only vs. 20% conventional only1
 Cost/diagnosis is 26% less than conventional testing2
1
Krahn AD, et al. Circ. 2001;104:46-51. 2Krahn AD, et al. JACC. 2003;42:495-501.
Conventional EP Testing in Syncope
 Greater diagnostic value in older patients or those with SHD

 Less diagnostic value in healthy patients without SHD
 Useful diagnostic observations:
• Inducible monomorphic VT
• SNRT > 3000 ms or CSNRT > 600 ms
• Inducible SVT with hypotension
• HV interval ≥ 100 ms (especially in absence of inducible VT)
• Pacing induced infra-nodal block
Benditt D. In: Topol E, ed. Textbook of Cardiovascular Medicine. Lippencott;2002:1529-1542.

Lu F, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.
Diagnostic Limitations of EPS
 Difficult to correlate spontaneous events and

laboratory findings
 Positive findings1
• Without SHD: 6-17%
• With SHD: 25-71%
 Less effective in assessing bradyarrhythmias
than tachyarrhythmias2
 EPS findings must be consistent with clinical history
• Beware of false positive
Linzer M, et al. Ann Int Med. 1997;127:76-86.

1
Lu F, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.
2
ISSUE
International Study of Syncope of Uncertain Etiology
 Multicenter, international, prospective study

 Analyzed the diagnostic contribution of an ILR in
three predefined groups of patients with syncope of
uncertain origin:
1) Isolated syncope: No SHD, Normal ECG1
• Negative tilt
• Positive tilt
2) Patients with heart disease and negative EP test2
3) Patients with bundle branch block and negative EP test3
1
Moya A. Circulation. 2001; 104:1261-1267.
2
Menozzi C, et al. Circulation. 2002;105:2741-2745.
3
Brignole M, et al. Circulation. 2001;104:2045-2050.
ISSUE
Patients with Isolated Syncope and Tilt-Positive Syncope
111 Patients with Syncope

No SHD, Normal ECG
Tilt Test Followed by

Insertable Loop Recorder
82: Tilt-Negative
29: Tilt-Positive
“Isolated Syncope”
Follow-Up to Recurrent
Spontaneous Episode
Moya A. Circulation.
2001;104:1261-1267.
ISSUE
Isolated Syncope vs. Tilt-Positive Syncope
Conclusions
 Results similar in the two arms, including syncope
recurrence and ECG correlation
 Tilt-negative patients had as many bradycardias (18%) as
tilt-positive patients (21%)
 Most frequent finding was asystole secondary to progressive
sinus bradycardia, suggesting a neuro-mediated origin
 Homogeneous findings from tilt-negative and tilt-positive
infer low sensitivity of tilt-testing
Moya A. Circulation. 2001;104:1261-1267.

ISSUE
Patients with Heart Disease and a Negative EP Test
35 Pts with Heart Disease

and Insertable Loop Recorder
Syncope: 6 Pts (17%) Pre-Syncope: 13 Pts (37%)
ECG-Documented: 6 Pts (17%) ECG-Documented: 8 Pts (23%)
AV block + asystole: 1 Sustained VT: 1

A.Fib + asystole: 1 Parox. A.Fib/AT: 1
Sinus arrest: 1 Post tachycardia pause: 1
Sinus tachycardia: 1 No rhythm variations: 4
Rapid A.Fib: 2 Sinus tachycardia: 1

ISSUE
Patients with Heart Disease and a Negative EP Test
Conclusions
 Patients with unexplained syncope, overt heart disease, and
negative EP study had a favorable medium-term outcome
 Mechanism of syncope was heterogeneous
 Ventricular tachyarrhythmia was unlikely
 “ILR-guided strategy seems reasonable, with specific therapy
safely delayed until a definite diagnosis is made.”

ISSUE
Patients with Bundle Branch Block and Negative EP Test
52 Pts with BBB

and Insertable Loop Recorder
Syncope: Stable AVB: ILR-Detected Death:

22 Pts (42%)* 3 Pts (6%) Pre-Syncope: 1 Pt (2%)
2 Pts (4%)**
ILR-Detected: 19 Not Detected: 3

AVB: 2 (4%)
AVB: 12 (63%)
SA: 4 (21%)
Asystole-undefined: 1 (5%)
NSR: 1 (5%)
Sinus tachy: 1 (5%)
* 5 of these also had ≥1 presyncope

Brignole M., ET AL.,Circulation. 2001;104:2045-2050. ** Drop-out before primary-end point
ISSUE
Patients with Bundle Branch Block and Negative EP Test
Conclusion:
 In patients with BBB and negative EP study, most syncopal
recurrences have a homogeneous mechanism that is
characterized by prolonged asystolic pauses mainly attributable
to sudden-onset paroxysmal AV block
Brignole M. Circulation. 2001;104:2045-2050.

Section III:
Specific Conditions and Treatment
Specific Conditions
 Cardiac arrhythmia
• Brady/Tachy
• Long QT syndrome
• Torsade de pointes
• Brugada
• Drug-induced
 Structural cardio-pulmonary
 Neurally-mediated
• Vasovagal Syncope (VVS)

• Carotid Sinus Syndrome (CSS)
 Orthostatic
Cardiac Syncope
 Includes cardiac arrhythmias and SHD

 Often life-threatening
 May be warning of critical CV disease
• Tachy and brady arrhythmias
• Myocardial ischemia, aortic stenosis, pulmonary hypertension,
aortic dissection
 Assess culprit arrhythmia or structural abnormality aggressively
 Initiate treatment promptly

“…cardiac syncope can be a harbinger of sudden death.”
 Survival with and 1.0

without syncope
0.8
 6-month mortality rate
Probability of Survival
of greater than 10%
0.6
 Cardiac syncope
doubled the risk
0.4
of death
No Syncope
Vasovagal and
 Includes cardiac 0.2 Other Causes
Cardiac Cause
arrhythmias and SHD
0 5 10
0.0 15 Follow-Up (yr)
Soteriades ES, et al. N Engl J Med. 2002;347:878.

Syncope Due to Structural Cardiovascular Disease:
Principle Mechanisms
 Acute MI/Ischemia  Pulmonary embolus/

pulmonary hypertension
• 2° neural reflex bradycardia –
Vasodilatation, arrhythmias, • Neural reflex, inadequate
low output (rare) flow with exertion
 Hypertrophic cardiomyopathy  Valvular abnormalities
• Limited output during exertion • Aortic stenosis – Limited output,
(increased obstruction, greater neural reflex dilation in periphery
demand), arrhythmias, neural
reflex • Mitral stenosis, atrial myxoma –
Obstruction to adequate flow
 Acute aortic dissection
• Neural reflex mechanism,
pericardial tamponade

Syncope Due to Cardiac Arrhythmias
 Bradyarrhythmias
• Sinus arrest, exit block
• High grade or acute complete AV block
• Can be accompanied by vasodilatation (VVS, CSS)
 Tachyarrhythmias
• Atrial fibrillation/flutter with rapid ventricular rate
(eg, pre-excitation syndrome)
• Paroxysmal SVT or VT
• Torsade de pointes

ILR Recordings
CASE: 83 year-old woman with CASE: 28 year-old man presents

syncope due to bradycardia: to ER multiple times after falls
Pacemaker implanted. resulting in trauma. VT: Ablated
and medicated.
Reveal ® ILR recordings; Medtronic data on file.

Cardiac Rhythms During Unexplained Syncope
Composite: N=133 to 7109
Bradycardia
16% No Recurrence
(11-21%) 36%
(31-48%)
Arrhythmia
22%
(13-32%)
Tachycardia 6%
(2-11%)
Other 11%
Normal Sinus Rhythm
31%
(17-44%)
Seidl K. Europace. 2000;2(3):256-262.

Krahn AD. PACE. 2002;25:37-41.
Medtronic ILR Replacement Data. FY03, 04. On file.
Long QT Syndromes
 Mechanism
• Abnormalities of sodium and/or potassium channels
• Susceptibility to polymorphic VT (Torsade de pointes)
 Prevalence
• Drug-induced forms – Common
• Genetic forms – Relatively rare, but increasingly being recognized
• “Concealed” forms:
− May be common
− Provide basis for drug-induced torsade
Schwartz P, Priori S. In: Zipes D and Jalife J, eds. Cardiac Electrophysiology. Saunders;2004:651-659.
Syncope: Torsade de Pointes
From the files of DG Benditt, MD. U of M Cardiac Arrhythmia Center

Long QT Syndromes: 12-Lead ECG

Drug-Induced QT Prolongation
(List is continuously being updated)
 Antiarrhythmics  Antibiotics
• Class IA ...Quinidine, • Erythromycin, Pentamidine,
Procainamide, Disopyramide Fluconazole, Ciprofloxacin and
its relatives
• Class III…Sotalol, Ibutilide,
Dofetilide, Amiodarone, NAPA*  Nonsedating antihistamines
 Antianginal Agents • Terfenadine*, Astemizole
• Bepridil*  Others
 Psychoactive Agents • Cisapride*, Droperidol,
Haloperidol
• Phenothiazines, Amitriptyline,
Imipramine, Ziprasidone
*Removed from U.S. Market

Treatment of Long QT
 Suspicion and recognition are critical

 Emergency treatment
• Intravenous magnesium
• Pacing to overcome bradycardia or pauses
• Isoproterenol to increase heart rate and shorten repolarization
• ICD if prior SCA or strong family history
• If drug induced:
− Reverse bradycardia
− Withdraw drug
− Avoid ALL long-QT provoking agents
• If genetic:
− Avoid ALL long-QT provoking agents
 For more information visit www.longqt.org
Schwartz P, Priori S. In: Zipes D and Jalife J, eds. Cardiac Electrophysiology. Saunders;2004:651-659.
Treatment of Syncope
Due to Bradyarrhythmia
 Class I indication for 0.4 nV

0.2
pacing using dual 08:23:21 0.0
chamber system -0.2

-0.4
wherever possible :21 :22 :23 :24 :25 :26 :27 :28 :29
0.4
0.2
 Ventricular pacing in 8:23:29 0.0

-0.2
atrial fibrillation with -0.4
slow ventricular
:29 :30 :31 :32 :33 :34 :35 :36 :37
0.4
0.2
response 08:23:37 0.0
-0.2
-0.4
:37 :38 :39 :40 :41 :42 :43 :44 :45
ACC/AHA/NASPE 2002 Guideline Update. Circ. 2002;106:2145-2161.

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 for paroxysmal AF
• Atrial flutter – Ablate the IVC-TV isthmus of the re-entrant circuit
for ‘typical’ flutter
 Ventricular tachyarrhythmias
• Ventricular tachycardia – ICD or ablation where appropriate
• Torsade de pointes – Withdraw offending drug or implant ICD
(long QT/Brugada/short QT)
 Drug therapy may be an alternative in many cases

Neurally-Mediated Reflex Syncope
 Vasovagal Syncope (VVS)

 Carotid Sinus Syndrome (CSS)
 Situational syncope
• Post-micturition
• Cough
• Swallow
• Defecation
• Blood drawing, etc.

Pathophysiology
Autonomic
Nervous
System
Benditt D, et al. Neurally mediated syncope:

Pathophysiology, investigations and treatment. Blanc JJ,
et al. eds. Futura. 1996.
VVS
Clinical Pathophysiology
 Neurally-mediated physiologic reflex mechanism with

two components:
1. Cardioinhibitory (↓ HR)
2. Vasodepressor (↓ BP) despite heart beats, no significant
BP generated
 Both components are usually present 1
Wieling W, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;11-22.
VVS
Incidence
 Most common form of syncope

• 8% to 37% (mean 18%) of syncope cases
 Depends on population sampled
• Young without SHD, ↑ incidence
• Older with SHD, ↓ incidence
Linzer M, et al. Ann Intern Med. 1997;126:989.

VVS vs. CSS
 In general:
• VVS patients younger than CSS patients
• Ages range from adolescence to older adults
(median 43 years)
Linzer M, et al. Ann Intern Med. 1997;126:989.

VVS
Recurrences
 35% of patients report syncope recurrence during follow-up

≤3 years1
 Positive HUT with >6 lifetime syncope episodes: recurrence risk
>50% over 2 years2
1000
> 75%
800
Total Number of Syncopal Episodes
Two Year Risk
100
50
25
50-75%
8
4
25-50%
2
1 < 25%
1 2 3 6 24 84 480
Months Since Symptoms Began

1
Savage D, et al. STROKE. 1985;16:626-29.
2
Sheldon R, et al. Circulation. 1996;93:973-81.
VVS
Spontaneous
16 year-old male, healthy, athletic, monitored for fainting.
16.3
sec
Continuous Tracing 1 sec

VVS
Diagnosis
 History and physical exam,

ECG and BP
 Head-Up Tilt (HUT) – Protocol:
60° - 80°
• Fast > 2 hours
• ECG and continuous blood
pressure, supine, and upright
• Tilt to 70°, 20 minutes
• Isoproterenol/Nitroglycerin if
necessary
• End point – Loss of consciousness
Benditt D, et al. JACC. 1996;28:263-275.

VVS
General Treatment Measures
 Optimal treatment  Long-term prevention

strategies for VVS are • Tilt training
a source of debate
• Education
 Treatment goals
• Diet, fluids, salt
• Acute intervention
• Support hose
− Physical maneuvers, eg,
crossing legs or tugging arms • Drug therapy
− Lowering head • Pacing
− Lying down

VVS
Tilt Training Protocol
 Objectives
• Enhance orthostatic tolerance
• Diminish excessive autonomic
reflex activity
• Reduce syncope
susceptibility/recurrences
 Technique
• Prescribed periods of upright
posture against a wall
• Start with 3-5 min BID
• Increase by 5 min each
week until a duration of
30 min is achieved
Reybrouck T, et al. PACE. 2000;23(4 Pt. 1):493-498.

VVS
Tilt Training: Clinical Outcomes
 Treatment of recurrent VVS

 Reybrouck, et al.*: Long-term study
• 38 patients performed home tilt training
• After a period of regular tilt training, 82% remained free of
syncope during the follow-up period
• However, at the 43-month follow-up, 29 patients had abandoned
the therapy
• Conclusion: The abnormal autonomic reflex activity
of VVS can be remedied. Compliance may be an issue.
*Reybrouck T, et al. PACE. 2000;23:493-498.

VVS
Tilt Training: Clinical Outcomes
 Foglia-Manzillo, et al.*: Short-term study

• 68 patients
– 35 tilt training
– 33 no treatment (control)
• Tilt table test conducted after 3 weeks
• 19 (59%) of tilt trained and 18 (60%) of controls had a positive test
• Tilt training was not effective in reducing tilt testing positivity rate
• Poor compliance in the majority of patients with recurrent VVS
*Foglio-Manzillo G, et al. Europace. 2004;6:199-204.

VVS
Pharmacologic Treatment
 Fludrocortisone
 Beta-adrenergic blockers
• Preponderance of clinical evidence
suggests minimal benefit1
 SSRI (Selective Serotonin
Re-Uptake Inhibitor)
• 1 small controlled trial2
 Vasoconstrictors
• 1 negative controlled trial
(etilefrine)3
• 2 positive controlled trials
(midodrine)4,5
1
2
Di Girolamo E, et al. JACC. 1999;33:1227-1230. Ward C, et al. Heart. 1998;79:45-49.
4
3
Raviele A, et al. Circ. 1999;99:1452-1457. Perez-Lugones A, et al. J Cardiovasc Electrophysiol. 2001;12(8):935-938.
5
Midodrine for VVS
100
80
Symptom-Free Interval
60 Midodrine
Fluid
40
20
p < 0.001
0
0 20 40 60 80 100 120 140 160 180
Months
Perez-Lugones A, Schweikert R, Pavia S, et al. J Cardiovasc Electrophysiol. 2001;12(8):935-938.

The Role of Pacing as Therapy for Syncope
 VVS with +HUT and cardioinhibitory response:

Class IIb indication for pacing
 Three randomized, prospective trials reported benefits
of pacing in select VVS patients:
• VPS I1
• VASIS2
• SYDIT3
 Subsequent study results less clear
• VPS II4
• Synpace5
• INVASY6
1
Connolly SJ. J Am Coll Cardiol. 1999;33:16-20. 4
Connolly S. JAMA. 2003;289:2224-2229.
2
Sutton R. Circulation. 2000;102:294-299. 5
Giada F. PACE . 2003;26:1016 (abstract).
3
Ammirati F. Circ. 2001;104:52-57. 6
Occhetta E, et al. Europace. 2004;6:538-547.
VPS I
(North American Vasovagal Pacemaker Study)
 Objective: To evaluate pacemaker therapy for severe recurrent

vasovagal syncope
 Randomized, prospective, single center
 N=54 patients
• 27: DDD pacemaker with rate drop response
• 27: No pacemaker
 Inclusion: Vasodepressor response
 Primary outcome: First recurrence of syncope
Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.

VPS I
(North American Vasovagal Pacemaker Study)
100
90
80
No Pacemaker (PM)
Cumulative Risk (%)
70
60
2P=0.000022
50
40
30
Pacemaker
20
10
0 3 6 9 12 15
Time in Months
Results:
 6 (22%) with PM had recurrence vs. 19 (70%) without PM
 84% RRR (2p=0.000022)
Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.

VASIS
(VAsovagal Syncope International Study)
 Objective: To evaluate pacemaker therapy for severe

cardioinhibitory tilt-positive neurally mediated syncope
 Randomized, prospective, multi-center
 N=42 patients
• 19: DDI pacemaker (80 bpm) with rate hysteresis (45 bpm)
• 23: No pacemaker
 Inclusion: Positive cardioinhibitory response
Sutton R. Circulation. 2000;102:294-299.

VASIS
(VAsovagal Syncope International Study)
Pacemaker (PM)
100
80
% Syncope-Free
p=0.0004
60
40
No Pacemaker
20
0 2 3 4 5 6
Years
Results:
 1 (5%) with PM had recurrence vs. 14 (61%) without PM
Sutton R. Circulation. 2000;102:294-299.

SYDIT
(SYncope DIagnosis and Treatment)
 Objective: To compare the effects of cardiac pacing

with pharmacological therapy in patients with
recurrent vasovagal syncope
 Randomized, prospective, multi-center
 N=93 patients
• 47: Atenolol 100 mg/d
 Inclusion: Positive HUT with relative bradycardia
Ammirati F. Circulation. 2001;104:52-57.

SYDIT
(SYncope DIagnosis and Treatment)
1.0
Pacemaker (PM)
0.9
% Syncope-Free
0.8 p=0.0032
0.7 Drug
0.6
0 100 200 300 400 500 600 700 800 900 1000
Time (Days)
Results:
 2 (4%) with PM had syncope recurrence vs. 12 (26%) without PM
Ammirati F. Circulation. 2001;104:52-57.

VPS II
(Vasovagal Pacemaker Study II)
 Objective: To determine if pacing therapy reduces the risk

of syncope in patients with vasovagal syncope
 Randomized, double-blind, prospective, multi-center
 N=100 patients
• 52: Only sensing without pacing
 Inclusion: Positive HUT with (HRxBP) < 6000/min x mm Hg
Connolly S. JAMA. 2003;289:2224-2229.

VPS II
(Vasovagal Pacemaker Study II)
1.0
0.8
Cumulative Risk
0.6
Only Sensing Without
Pacing (ODO)
0.4
0.2 Dual Chamber Pacing

(DDD)
0 1 2 3 4 5 6
Months Since Randomization
Results:
 33% with pacing had recurrence vs. 42% with only sensing
(not statistically significant)
Connolly S. JAMA. 2003;289:2224–2229.
SYNPACE
(Vasovagal SYNcope and PACing)
 Objective: To determine if pacing therapy will reduce syncope

relapses in patients with recurrent vasovagal syncope,
compared to those with a pacemaker programmed to OFF
 Randomized, double-blind, prospective, multi-center,
placebo-controlled
 N=29 patients
• 16: DDD PM with rate drop response programmed ON
• 13: PM programmed OFF (OOO mode)
 Inclusion: Recurrent VVS and +HUT with asystolic
or mixed response
Raviele A.. Europace. 2001;3:336–341.

Raviele A, et al. Eur Heart J. 2004;25:1741-1748.
SYNPACE
(Vasovagal SYNcope and PACing)
1.0
0.9 p=0.58
0.8
% Syncope-Free
0.7
0.6 Pacemaker OFF
0.5
Pacemaker ON
0.4
0.3
0.2
0.1
0.0
0 200 400 600 800 1000
Days Since Randomization
Results:
 50% with pacing ON had recurrence vs. 38% with pacing OFF
(not statistically significant)
Raviele A, et al. Eur Heart J. 2004;25:1741-1748.
INVASY
(INotropy Controlled Pacing in VAsovagal Syncope)
 Objective: To evaluate Closed Loop Stimulation (CLS), a form of

rate-adaptive pacing using RV impedance, in preventing
recurrence of VVS
 Randomized, prospective, single-blind, multi-center
 N=50 patients
• 41: CLS therapy
• 9: Control (pacemaker programmed in DDI)
 Inclusion: Recurrent VVS and +HUT with cardioinhibition
 Primary outcome: Recurrence of two VVSs during
a minimum of 1 year of follow-up

INVASY
(INotropy Controlled Pacing in VAsovagal SYncope)
100
Closed Loop Stimulation (CLS)
0
% Syncope-Free
60
P < 0.0001
40
Control (DDI only)

20
3m 6m 9m 1y 2y 3y
Time Since Randomization
Results:
 Patients with CLS had no syncope recurrence and improved quality of life

Role of Pacing as Therapy for Syncope: Summary
 Three earlier studies single blind – Bias?

 Pacemaker implantation may modulate reflex syncope
and autonomic responses1
 Study results may differ based on pre-implant selection
criteria and tilt-testing techniques
 Pacing therapy is effective in some but not all (cardioinhibition
vs. vasodepression)
 In five pacing studies, syncope recurred in 33/156
(21%) of paced patients, 72/162 (44%) in non-paced
patients (p<0.000)2
Kapoor W. JAMA. 2003;289:2272-2275.

1
Brignole M, et al.. Europace. 2004;6:467-537.

2
CSS
Carotid Sinus Syndrome
 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
 Prevalence higher than previously believed
 Carotid Sinus Hypersensitivity (CSH)
• No symptoms
• No treatment
Kenny RA, et al. J Am Coll Cardiol. 2001;38:1491-1496.

Sutton R. In: Neurally Mediated Syncope: Pathophysiology, Investigation and Treatment. Blanc JJ, et al. eds. Armonk, NY: Futura;1996:138.
CSS
Etiology
 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 Carotid Sinus
activity and diminution of
sympathetic tone results in
bradycardia and vasodilatation
Falls:
Incidence, Recurrence, CSH*
50% 1
% of Population
30% 1
23% 2
Incidence Recurrence CSH* Present

> Age 65 in Fallers > Age 50
Presenting at ER
*Carotid Sinus Hypersensitivity
1
J Am Geriatr Soc. 1995.
2
Richardson D, et al. PACE. 1997;20:820.
CSS
Role of Pacing – Syncope Recurrence Rate
 Class I indication for pacing

(AHA and BPEG) 57%
 Limit pacing to CSS
% Recurrence
that is:
• Cardioinhibitory
• Mixed
 DDD/DDI superior to VVI %6
• Mean follow-up = 6 months
Brignole M, et al. Eur JCPE. 1992;4:247-254.

SAFE PACE
Syncope And Falls in the Elderly – Pacing And Carotid Sinus Evaluation
 Objective  Results
• Determine whether cardiac • More than 1/3 of adults over
pacing reduces falls in 50 years presented to the
older adults with carotid Emergency Department
sinus hypersensitivity because of a fall
 Randomized controlled • With pacing, falls  70%
trial (N=175) • Syncopal events  53%
• Adults > 50 years, • Injurious events  70%
non-accidental fall,
positive CSM
• Pacing (n=87) vs.
No Pacing (n=88)
Kenny RA. J Am Coll Cardiol. 2001;38:1491-1496.

SAFE PACE
 Conclusions
• Strong association between non-accidental falls and
cardioinhibitory CSH
• These patients usually not referred for cardiac assessment
• Cardiac pacing significantly reduced subsequent falls
• CSH should be considered in all older adults who have
non-accidental falls
Kenny RA, J Am Coll Cardiol. 2001; 38:1491-1496.

Orthostatic Hypotension
 Etiology  Secondary autonomic failure

 Drug-induced (very common) • Diabetes
• Diuretics • Alcohol
• Vasodilators • Amyloid
 Primary autonomic failure

• Multiple system atrophy
• Parkinson’s Disease
• Postural Orthostatic Tachycardia
Syndrome (POTS)

Treatment Strategies for Orthostatic Intolerance
 Patient education, injury avoidance

 Hydration
• Fluids, salt, diet
• Minimize caffeine/alcohol
 Sleeping with head of bed elevated
 Tilt training, leg crossing, arm pull
 Support hose
 Drug therapies
• Fludrocortisone, midodrine, erythropoietin
 Tachy-Pacing (probably not useful)

Section IV:
Special Issues
Syncope:
Diagnostic Testing in Hospital Strongly Recommended
 Suspected/known ‘significant’ heart disease

 ECG abnormalities suggesting potential life-threatening
arrhythmic cause
 Syncope during exercise
 Severe injury or accident
 Family history of premature sudden death

SEEDS:
Syncope Evaluation in the Emergency Department Study
Long-Term Clinical Outcomes
Survival Free from Death Survival Free from Recurrence
100% 100%
90% 90%
Syncope Unit Group Syncope Unit Group

80% Standard Care Group 80% Standard Care Group
P=0.30 P=0.72
70% 70%
0 1 2 0 1 2
Years Years
Results:
 Syncope unit improved diagnostic yield in the ED and reduced
hospital admission and length of stay
Shen W, et al. Circ. 2004;110(24):3636-3645.
The Integrated Syncope Unit
 To optimize the effectiveness of the evaluation and treatment

of syncope patients at a given center
 Best accomplished by:
• Cohesive, structured care pathway
• Multidisciplinary approach
• Core equipment available
• Preferential access to other tests or therapy
 Majority of syncope evaluations – Out-patient or day cases
Kenny RA, Brignole M. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:55-60.
1

2
Conclusion
 Syncope is a common symptom with many causes

 Deserves thorough investigation and appropriate treatment
 A disciplined approach is essential
 ESC guidelines offer current best practices

Challenges of Syncope
 Cost
 Quality of life implications
 Diagnosis and treatment
• Diagnostic yield and repeatability of tests
• Frequency and clustering of events
• Difficulty in managing/treating/controlling future events
• Appropriate risk stratification
• Complex etiology
Olshansky B. In: Grubb B and Olshansky B. eds. Syncope: Mechanisms and Management. Futura. 1998:15-71.
Brief Statement
Indications
9526 Reveal® Plus Insertable Loop Recorder
The Reveal Plus ILR is an implantable patient- and automatically activated monitoring system that records subcutaneous ECG and is indicated for
Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias
Patients who experience transient symptoms that may suggest a cardiac arrhythmia
6191 Activator
The Model 6191 Activator is intended for use in combination with a Medtronic Model 9526 Reveal Plus Insertable Loop Recorder.
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.
Potential Complications
Potential complications include, but are not limited to, body tissue rejection phenomena, including local tissue reaction, infection, device migration and
erosion of the device through the skin.
2090 Programmer
The Medtronic/Vitatron CareLink programmer system is comprised of prescription devices indicated for use in the interrogation and programming of
implantable medical devices. Prior to use, refer to the Programmer Reference Guide as well as the appropriate programmer software and implantable
device technical manuals for more information related to specific implantable device models. Programming should be attempted only by appropriately
trained personnel after careful study of the technical manual for the implantable device and after careful determination of appropriate parameter values
based on the patient's condition and pacing system used. The Medtronic/Vitatron CareLink programmer must be used only for programming implantable
devices manufactured by Medtronic or Vitatron.
See the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential
complications/adverse events. For further information, please call Medtronic at 1-800-328-2518 and/or consult Medtronic’s website at
www.medtronic.com. To learn more about syncope, visit www.fainting.com.
Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.

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Syncope

David G. Benditt, M.D. Richard Sutton, DScMed

Real or Apparent TLOC

Syncope Disorders Mimicking Syncope

Brignole M, et al. Europace, 2004;6:467-537.

 Self-limited loss of consciousness and postural tone

Brignole M, et al. Europace, 2004;6:467-537.

I. Etiology, Prevalence, Impact

Unexplained Causes = Approximately 1/3

 Acute intoxication (e.g., alcohol)

Brignole M, et al. Europace, 2004;6:467-537.

 40% will experience syncope

 Minor injury in 29%1

Inpatient Trend* Physician Office Visits**

*Syncope and collapse (ICD-9 Code:780.2) listed as + Not available

 74,813 hospital consults for

*Hospital Episode Statistics, Dept. of Health, Eng. 2002-2003.

 Estimated hospital costs exceeded $10 billion US1

Anxiety/ Alter Daily Restricted Change

Linzer M. J Clin Epidemiol. 1991;44:1037.

Linzer M. J Gen Int Med. 1994;9:181.

Mobility Usual Self-Care Pain/ Anxiety/

Rose M, et al. J Clin Epidemiol. 2000;53:1209-1216.

 Low mortality vs.

 Those who drive and have  If the patient has sufficient

 Distinguish true syncope from syncope mimics

Syncope Not Syncope

Certain Suspected Unexplained

Cardiac Neurally-Mediated or Frequent or Severe Single/Rare Confirm with

Cardiac Tests for Neurally- Tests for Neurally- No Further

Treatment Treatment Treatment Treatment

Brignole M, et al. Europace, 2004;6:467-537.

 Circumstances of recent event

 Method1  Absolute contraindications2

 Head-Up Tilt (HUT)

Brignole M, et al. Europace, 2004;6:467-537.

Event Recorders 7-30 Days

Brignole M, et al. Europace, 2004;6:467-537.

History, Physical Exam, ECG, Cardiac Massage

 EEG, Head CT, Head MRI

Brignole M, et al. Europace. 2004;6:467-537.

Brignole M, et al. Europace. 2004;6:467-537.

Click once on image to play video.

Carlos Morillo, MD, FRCPC

DG Benditt, MD. U of M Cardiac Arrhythmia Center

 Ongoing investigation  Seems to identify a unique

Brignole M. Heart. 2000;83:24-28.

Click once on black screen to play video.

Reveal® Plus ILR Typical Location of the

The ILR is an implantable patient – and automatically – activated

Click once on black screen to play video.

CASE: 56 year-old woman with CASE: 65 year-old man with

Medtronic data on file.

 Greater diagnostic value in older patients or those with SHD

Benditt D. In: Topol E, ed. Textbook of Cardiovascular Medicine. Lippencott;2002:1529-1542.

 Difficult to correlate spontaneous events and

Linzer M, et al. Ann Int Med. 1997;127:76-86.

 Multicenter, international, prospective study

111 Patients with Syncope

Tilt Test Followed by

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

35 Pts with Heart Disease

Syncope: 6 Pts (17%) Pre-Syncope: 13 Pts (37%)