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Syncope Approach

Diagnosis

and Treatment

Robert Satran MD

Transient Loss of Consciousness (TLOC)

Transient Loss of Consciousness (TLOC ) Classification

✓ Syncope

▪ Neurally-mediated reflex

syndromes

▪ Orthostatic hypotension

▪ Cardiac arrhythmias

▪ Structural card iovascular

d isease

Real or Apparent TLOC

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

Underly ing Mechanism Is

Transient Global Cerebral Hypoperfusion.

✓ Disorders Mimicking Syncope

▪ With loss of consciousness, i.e.

seizure d isorders, concussion

▪ Without loss of consciousness,

psychogenic “pseudo-syncope”

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


Etiology ,

Prevalence ,

Impact …

Causes of True Syncope

Orthostatic Cardiac

Arrhythmia

Structural

Cardio-

Pulmonary

✓ VVS

✓ CSS

✓ Situational

▪ Cough

▪ Post-Micturition

✓ Drug-Induced

✓ ANS Failure

▪ Primary

▪ Secondary

✓ Brady

▪ SN Dysfunction

▪ AV Block

✓ Tachy

▪ VT

▪ SVT

✓ Long QT Syndrome

✓ Acute MI

✓ Aortic Stenosis

✓ HCM

✓ Pulmonary HTN

✓ Aortic Dissection

Neurally-

Mediated

Syncope Mimics

✓ Acute intoxication (e.g., alcohol)

✓ Seizures

✓ Sleep d isorders

✓ Somatization d isorder (psychogenic pseudo-syncope)

✓ Trauma/ concussion

✓ Hypoglycemia

✓ Hyperventilation


Impact of Syncope

1. Kenny RA, Kapoor WN. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura; 2003:23-27.

2. Kapoor W. Medicine. 1990; 69:160-175.

3. Brignole M, et al. Europace. 2003; 5:293-298.

4. Blanc J-J, et al. Eur Heart J. 2002; 23:815-820.

5. Campbell A, et al. Age and Ageing. 1981; 10:264-270.

Impact of Syncope: US Trends

30

40

50

60

70

80

'96 '97 '98 '99 '00 '01 '02

500

600

700

800

900

Emergency Department Visits* Hospital Outpatient Visits* (000 s)

+

*Syncope and collapse (ICD-9 Code:780.2) listed as primary

reason for visit. NHAMCS 2002.

(000 s(

Quality of Life : UK Population Norms vs. Syncope Patients

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

0

13

25

38

50

Mobility

Self-Care

Anxiety/Depression

3 4

1

36

19

26

37

9

49

43

UK Population Norms

Patients with Syncope

%P

reval

ence

Syncope Mortality

✓ Low mortality vs. high

mortality

✓ Neurally-mediated

syncope vs. syncope

with a card iac 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]

Syncope and Driving a Vehicle

✓ Those who drive and have recurrent syncope risk their lives

and the lives of others

✓ Places considerable burden

on the physician

✓ Essential to know local laws and physician responsibilities

✓ Some states – Invasion of privacy to notify motor vehicle

department*

✓ Other states – Reporting

is mandatory* If the patient has sufficient warning

of impending syncope Driving may

be permitted

Diagnosis …

Diagnostic Objectives

✓ Distinguish true syncope from syncope mimics

✓ Determine presence of heart d isease

✓ 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 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 d isease, especially card iac

✓ Pertinent family history

▪ Cardiac d isease

▪ Sudden death

▪ Metabolic d isorders

✓ Past medical history

▪ Neurological history

▪ Syncope

Initial Exam: Thorough Physical

✓ Vital signs

▪ Heart rate

▪ Orthostatic blood pressure change

✓ Cardiovascular exam: Is heart d isease present ?

▪ ECG: Long QT, pre-excitation, conduction system d isease

▪ 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(

✓ Method 1

▪ Massage, 5-10 seconds

▪ Don’t occlude

▪ Supine and upright posture

(on tilt table)

✓ Outcome

▪ 3 second asystole and/ or 50

mmHg fall in systolic BP with

reproduction of symptoms =

Carotid Sinus Syndrome

✓ Absolute contraindications2

▪ Carotid bruit, known significant carotid

arterial d isease, previous CVA, MI last 3

months

✓ Complications 3

▪ Primarily neurological

▪ Less than 0.2%

▪ Usually transient

1Kenny RA. Heart. 2000; 83:564.

2Linzer M. Ann Intern Med. 1997; 126:989.

3Munro 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(


Diagnostic Assessment: Yields

Yield )%(

Initial Evaluation

History, Physical Exam, ECG, Cardiac Massage

38-40

Other Tests/Procedures

Head-Up Tilt Test 27

External Cardiac Monitoring 5-13

Insertable Loop Recorder (ILR( 43

EP Study <2-5

Exercise Test 0.5

EEG 0.3-0.5

MRI NA

Neurological Tests : Rarely Diagnostic for Syncope

✓ EEG, Head CT, Head

MRI

✓ May help d iagnose

seizure


Head-Up Tilt Test (HUT(

✓ Protocols vary

✓ Useful as d iagnostic ad junct

in atypical syncope cases

✓ Useful in teaching patients

to recognize prodromal symptoms

✓ Not useful in assessing treatment


Head-Up Tilt Test: ECG Leads and Intra-Arterial Pressure Tracing

2

1

Insertable Loop Recorder (ILR(

Insertable Loop Recorder (ILR(

✓ The ILR is an implantable patient – and automatically – activated

monitoring system that records subcutaneous ECG .

✓ Indicated for:

▪ Patients with clinical syndromes or situations at increased risk of

cardiac arrhythmias

▪ Patients who experience transient symptoms that may suggest a

card iac arrhythmia

Specific Conditions and Treatment …

Specific Conditions ✓ Cardiac arrhythmia

▪ Brady/ Tachy

▪ Long QT syndrome

▪ Torsade de pointes

▪ Brugada

▪ Drug-induced

✓ Structural card io-pulmonary

✓ Neurally-mediated

▪ Vasovagal Syncope (VVS(

▪ Carotid Sinus Syndrome (CSS(

✓ Orthostatic

Cardiac Syncope

✓ Includes card iac arrhythmias and SHD

✓ Often life-threatening

✓ May be warning of critical CV disease

▪ Tachy and brady arrhythmias

▪ Myocard ial ischemia, aortic stenosis, pulmonary hypertension ,

aortic d issection

✓ Assess culprit arrhythmia or structural abnormality aggressively

✓ Initiate treatment promptly


“Cardiac Syncope …. A Harbinger of Sudden Death .”

✓ Survival with and without syncope

✓ 6- month mortality rate > 10%

✓ Cardiac syncope doubled risk

of death

✓ Includes card iac arrhythmias and

SHD

Soteriades ES, et al. N Engl J Med. 2002; 347:878.

✓ Acute MI/ Ischemia

▪ 2° neural reflex bradycard ia – Vasodilatation,

arrhythmias ,

low output (rare(

✓ Hypertrophic card iomyopathy

▪ Limited output during exertion (increased obstruction,

greater demand), arrhythmias, neural reflex

✓ Acute aortic d issection

▪ Neural reflex mechanism, pericard ial tamponade

Syncope d/t Structural Cardiovascular Disease

Syncope d/t Structural Cardiovascular Disease

✓ Pulmonary embolism/ pulmonary HTN

▪ Neural reflex, inadequate

flow with exertion

✓ Valvular abnormalities

▪ Aortic stenosis – Limited output, neural reflex

d ilation in periphery

▪ Mitral stenosis, atrial myxoma – Obstruction to

adequate flow

Syncope d/t Cardiac Arrhythmias

✓ Bradyarrhythmias ▪ Sinus arrest, exit block

▪ High grade or acute complete AV block

▪ Can be accompanied by vasodilatation (VVS, CSS(

✓ Tachyarrhythmias ▪ Atrial fibrillation/ flu tter with rapid ventricular rate

)eg, pre-excitation syndrome(

▪ Paroxysmal SVT or VT

▪ Torsade de pointes


ILR Recordings

CASE: 27 year-old man presents to ER

multiple times after falls resulting in

trauma .

VT: Ablated and medicated .

CASE: 83 year-old woman with syncope

due to bradycard ia :

Pacemaker implanted .

Cardiac Rhythms During Unexplained Syncope

Seidl K. Europace. 2000;2(3): 256-262.

Krahn AD. PACE. 2002; 25:37-41 .

No Recurrence 36%

(31-48%)

Normal Sinus Rhythm 31%

(17-44%)

Other 11%

Arrhythmia 21%

(13-32%)

Tachycardia 6%

(2-11%)

Bradycardia 15%

(11-21%)

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 d rug-induced torsade

Schwartz P, Priori S. In: Z ipes D and Jalife J, eds .

Cardiac Electrophysiology. Saunders; 2004:651-659.

Syncope: Torsade de Pointes

Drug-Induced QT Prolongation

✓ Antiarrhythmics

▪ Class IA ...Quinid ine,

Procainamide, Disopyramide

▪ Class III…Sotalol, Amiodarone

✓ Psychoactive Agents

▪ Phenothiazines, Amitriptyline,

Imipramine, Ziprasidone

✓ Antibiotics

▪ Erythromycin, Pentamidine,

Fluconazole, Ciprofloxacin and its

relatives

✓ Nonsedating antihistamines

▪ Terfenadine*, Astemizole

✓ Others

▪ Cisapride*, Droperidol,

Haloperidol

…List is continuously being updated

Treatment of Long QT ✓ Suspicion and recognition are critical

✓ Emergency treatment

▪ Intravenous magnesium

▪ Pacing to overcome bradycard ia or pauses

▪ Isoproterenol to increase heart rate and shorten repolarization

▪ ICD if prior SCA or strong family history

▪ If d rug induced :

▪ Reverse bradycard ia

▪ 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 pacing using dual chamber system

wherever possible

✓ Ventricular pacing in atrial fibrillation with slow

ventricular response

ACC/AHA/NASPE 2002 Guideline

Update. Circ. 2002; 106:2145-2161.

Treatment of Syncope Due to Tachyarrhythmia

✓ Atrial tachyarrhythmia

▪ 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 tachyarrhythmia

▪ Ventricular tachycard ia – 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

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

Wieling W, et al. In: Benditt D, et al .

The Evaluation and Treatment of Syncope.

Futura. 2003; 11-22.

1 2

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

1Savage D, et al. STROKE. 1985;16:626-29.

2Sheldon R, et al. Circulation. 1996;93:973-81.

• 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

800

50

100

25

8

4

2

1

1 2 3 6 24 84 480

Months Since Symptoms Began

Two Year Risk

Tota

l N

um

ber

of S

yncopal

Ep

iso

de

s

>75%

50-75%

25-50%

<25%

VVS Diagnosis

✓ History and physical exam, ECG and BP

✓ Head-Up Tilt (HUT) – Protocol :

▪ 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

strategies for VVS are

a source of debate

✓ Treatment goals

▪ Acute intervention

▪ Physical maneuvers, eg ,

crossing legs or tugging

arms

▪ Lowering head

▪ Lying down

✓ Long-term prevention

▪ Tilt training

▪ Education

▪ Diet, flu ids, salt

▪ Support hose

▪ Drug therapy

▪ Pacing

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

▪ 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

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

2Di Girolamo E, et al. JACC. 1999; 33:1227-1230.

3Raviele A , et al. Circ. 1999; 99:1452-1457.

4Ward C, et al. Heart. 1998; 79:45-49.

5Perez-Lugones A, et al. J Cardiovasc Electrophysiol .

2001;12(8:)935-938.

Midodrine for VVS

Perez-Lugones A, Schweikert R, Pavia S, et al.

J Cardiovasc Electrophysiol. 2001;12(8):935-938.

Months

p < 0.001

Sym

pto

m-F

ree I

nte

rval

180 160 140 120 100 80 60 40 20 0

100

80

60

40

20

0

Fluid

Midodrine

The Role of Pacing as Therapy for Syncope

✓ VVS with +HUT and card ioinhibitory response:

Class IIb ind ication 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

1Connolly SJ. J Am Coll Cardiol. 1999; 33:16-20.

2Sutton R. Circulation. 2000; 102:294-299.

3Ammirati F. Circ. 2001; 104:52-57.

4Connolly S. JAMA. 2003; 289:2224-2229.

5Giada F. PACE . 2003;26:1016 (abstract.)

6Occhetta 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 .

100

90

80

70

60

50

40

30

20

10

0

0 3 6 9 12 15

Time in Months

No Pacemaker (PM)

P=0.000022

Pacemaker Cum

ula

tive

Ris

k

)%(

Connolly SJ. J Am Coll Cardiol. 1999; 33:16-20 .

Results:

• 6 (22% ) with PM had recurrence vs. 19 (70%) without PM

• 84% RRR (p= 0.000022)

VPS I )North American Vasovagal Pacemaker

Study(

SYNPACE )Vasovagal SYNcope and PACing (

Raviele A, et al. Eur Heart J. 2004;25:1741-1748.

Results: 50% with pacing ON had recurrence vs. 38% with pacing OFF

)not statistically significant(

0.6

0.7

0.8

0.9

1.0

0 200 400 600 800 1000

Pacemaker OFF

%S

yncope-F

ree

p=0.58

0.5

0.4

0.3

0.2

0.1

0.0

Pacemaker ON

Days Since Randomization

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 ind ividuals

✓ 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.

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

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

✓ Increased afferent signals to

brain stem

✓ Reflex increase in efferent vagal activity

✓ Decrease of sympathetic tone

✓ BRADYCARDIA AND VASODILATATION

Falls: Incidence, Recurrence, CSH*

1 J Am Geriatr Soc. 1995.

2 Richardson D, et al. PACE. 1997; 20:820.

0

19

38

56

75

Incidence > Age 65 Recurrence CSH* Fallers > Age 50 in ER

30% 1

50% 1

23% 2

*Carotid Sinus Hypersensitivity

Orthostatic Hypotension Etiology

✓ Etiology

✓ Drug-induced (very common(

▪ Diuretics

▪ Vasodilators

✓ Primary autonomic failure

▪ Multiple system atrophy

▪ Parkinson’s Disease

▪ Postural Orthostatic Tachycardia Syndrome (POTS(

✓ Secondary autonomic failure

▪ Diabetes

▪ Alcohol

▪ Amyloid


Treatment Strategies for Orthostatic Intolerance

✓ Patient education, injury avoidance

✓ Hydration

▪ Fluids, salt, d iet

▪ 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(


Diagnostic Testing in Hospital Strongly Recommended !

✓ Suspected / known ‘significant’ heart d isease

✓ ECG abnormalities suggesting potential life-threatening

arrhythmia

✓ Family history of premature sudden death

✓ Syncope during exercise

✓ Severe injury or accident

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

Thank You !