SYNCOPE

Nora Goldschlager, M.D.MACP, FACC, FAHA, FHRS

Cardiology – San Francisco General HospitalUCSF

Disclosures: None

SCOPE OF THE PROBLEM

•Cumulative lifetime incidence in general population up to 35%

•1% of all hospital admissions•3% of all ER visits; up to 65% are vasovagal•6% incidence in institutionalized elderly•Prevalence: 7 - 47% in young, healthy

subjects; unknown in elderly•Up to 30% of patients may have no

diagnosis established at hospital discharge

•6% annual mortality if no cause established•12 - 25% recurrence

Kapoor Medicine 69:1990 N = 433 Sudden death: 37%

Mo

rtal

ity

%

50

40

30

20

10

0

Cardiac

Noncardiac

Unknown

Yr. of FU: 0 1 2 3 4 5No. at risk: 433 380 349 295 179 44

SURVIVAL IN SYNCOPAL PATIENTS

Follow-up (yr)Soteriades et al NEJM 2002;347:878 (Framingham) N = 822/7814

0 5 10 15 20 25

Pro

bab

ility

of

surv

ival 1.0

.8

.6

.4

.2

0

No syncope

Vasovagal & other causes (OH, med Rx)

Unknown cause

Neurologic cause

Cardiac cause

PREVALENCE OF SYNCOPE BY AGE

50

40

30

20

10

0

Ganzeboom et al AJC 4.15.03

Pre

vale

nce

(%

)

Age (yrs)

MalesFemales

0 7 14 21

YOUNGER ADULTS ELDERLY

15% 15%

40%30%30% 25%

15%30%

Vasovagal

Undetermined

Cardiogenic

Other causes

OH, situational,seizures, drugs

1° arrhythmia

OH, CSS, situational, seizures, drugs

1° arrhythmia,LV obstruction

ETIOLOGY OF FIRST SYNCOPEIN PATIENTS > 65 YEARS

%• Reflex-mediated

(VVS, CSS, situational) 13-30%• Orthostatic 12• Cardiac

Arrhythmic 8Nonarrhythmic 3

• Drug-induced 8• CNS 6• Unexplained 49

Roussanov et al, Am J Geriatric Cardiol 2007;16:249 N=304 (VA patients)

FEATURES OF UNEXPLAINEDSYNCOPE IN OLDER PATIENTS

• High incidence of comorbid conditions• 24% recurrence rate• Concurrent BP and HF Rx increases

susceptibility to + HUT• Only 9% had an etiology established

during follow-up• Lower diagnostic yield of history and

tests compared in younger patients

Roussanov et al, Am J Geriatric Cardiol 2007;16:249 N=304 (VA patients)

PROGNOSIS IN UNEXPLAINED SYNCOPEIN PATIENTS > 65

Pro

po

rtio

n o

f p

ts a

live

1.0

.75

.50

.25

00 1 2 3

Yrs FU

Roussanov et al Am J Geriatric Cardiol 2007; 16:249 N = 304 VA pts

Control

Syncope

EVALUATION OF SYNCOPE: PERTINENT HISTORY

• Precipitating factors- Posture changes (orthostatic hypotension)- Cough, swallowing, micturition, defecation

(“situational” syncope)- Exercise (consider aortic stenosis, HOCM, VT)- Head turning, Valsalva (suggests carotid

sinus syndrome)• Prodromal symptoms• Speed of onset and recovery (prolonged

recovery suggests vasovagal syncope)• Aura (suggests seizure)• Hx heart disease (predicts cardiac syncope:

95% specificity <50%>)

NATURAL HISTORY OF AORTIC STENOSIS%

Su

rviv

al

100

75

50

25

0

Onset of SxWith AVR

Without AVR

Asx stage

CHFAnginaSyncope

10 20 30Years

EVALUATION OF SYNCOPE: PERTINENT HISTORY• Drugs

- Diuretics ( hypokalemia, hypomagnesemia)- Digitalis (AVB, VT-classically bidirectional)- Antihypertensives- Antiarrhythmic agents (proarrhythmia)- Ophthalmic -blockers- Antianginal medications (preload and afterload reduction)- QT prolonging drugs (www.torsades.org)- OTC drugs- Herbs- Illicit drugs, alcohol- β-blockers

• Family history of sudden death (congenital long QT syndrome, hypertrophic obstructive cardiomyopathy)

• Known rhythm abnormality (e.g., WPW)

Exercise-induced RVOT VT

Tussive bradycardia

Deglutition bradycardiaContinuous strips

CONGENITAL LQTS

• 1:10,000 is a gene carrier• 3-4,000 sudden deaths/yr, mostly young

patients• 10% sudden deaths in untreated patients• 30% of sudden or aborted sudden deaths

occur as 1st event• Female gender• About 10% have normal QTC; about 30%

have borderline QTC

CLUES TO ETIOLOGY OF SYNCOPE FROM PHYSICAL EXAMINATION

• Left ventricular impulse abnormalities suggesting past myocardial infarction

• Ventricular hypertrophy (need for AV synchrony)

• Ventricular gallops• Murmurs (aortic stenosis, hypertrophic

obstructive cardiomyopathy)• Pulmonary hypertension• Mitral valve prolapse

(PSVT, VT, autonomic dysfunction)• Carotid sinus massage indicating CSH

• Generally accepted contraindications - Carotid bruits- Prior endarterectomy- Prior TIA or CVA- Known cerebrovascular disease

• Responses to CSM- Bradycardia / asystole usually abrupt- Hypotension often not abrupt, and

outlasts the CSM- Complications (< 1%): TIA, transient

paresis, visual disturbances

CAROTID SINUS MASSAGE

CLUES TO ETIOLOGY OF SYNCOPE FROM 12-LEAD ECG

• Long QT interval• Prior MI (substrate for VT)• Epsilon wave, anterior (V1-3) T inversion, QRS

duration V1-3 / V4-6 > 1.2, suggesting RV dysplasia

• Brugada pattern• Short QT interval (with tall symmetric T waves)• Ectopy• Bradycardia• AV conduction delay / block• Bifascicular block• Ventricular hypertrophy (need for AV synchrony)

Epsilon wave of RV dysplasia

Marcus, Fontaine PACE 6.95

V1

V2

V3

RV DYSPLASIA

• Young pt• Can present as syncope or aborted

sudden death• ECG:

- Anterior T inversion V1-3

- Prominent anterior forces- RIVCD

- Delayed S wave V1-2

• MRI is usually (but not always) diagnostic (fat replacement)

RV dysplasia

BRUGADA SYNDROME

BRUGADA SYNDROME

OUTCOME IN PTS WITH BRUGADA ECGF

ree

of

even

ts(S

D, V

F)

1.0

.8

.6

.4

.2

0

Brugada et al Circulation 2002; 105:73 N = 334, all EPS 63% of syncopal pts had VT induced

Asymptomatic (57%)

Syncope (22%)

Sudden death (21%)

p = 0.00001

0 100 200 300Mos

Follow-up (mos)

Antzelevitch et al Circulation 2005; 111:659 N=258 (Registry)

PROGNOSIS OF SYNCOPE IN BRUGADA SYNDROME

Fre

e o

f A

pp

rop

ria

te IC

D R

x

1.0

.8

.6

.4

.2

0

Asymptomatic

Syncope

Sudden death

0 12 24 36 48 60

ROLE OF ECHOCARDIOGRAPHY IN SYNCOPE

• Aortic stenosis• Hypertrophic cardiomyopathy

(especially obstructive)• Regional wall-motion disorders

(substrate for VT)• Right ventricular dysplasia• Calcified mitral / aortic annulus

( AV block incidence)• Intracardiac tumor• Mitral valve prolapse• Repaired congenital heart disease• Normal echo

NONARRHYTHMIC CARDIAC SYNCOPE:OBSTRUCTION TO FLOW

• Aortic stenosis- LV baroceptor stimulation with

reflex peripheral vasodilation- Ventricular arrhythmias- Transmural ischemic injury with

LV dysfunction

• Hypertrophic obstructive cardiomyopathy• Tumor• Primary pulmonary hypertension, pulmonic stenosis• Pulmonary embolism

Syncope in aortic stenosisRecorded during syncopal spell. BP unobtainable.

Syncope in aortic stenosisLead III: During syncopal spell

SYNCOPE IN HYPERTROPHIC CARDIOMYOPATHY - 1

• Causes - SVT (especially AF)- VT- LV outflow tract gradient- Abnormal baroreceptor reflexes- Ischemia

• EP studies unreliable• -blockers, disopyramide and Ca++ channel

blockers do not reduce incidence of SD

SYNCOPE IN HYPERTROPHIC CARDIOMYOPATHY - 2

• ICD indicated for high risk patients

- Family hx syncope/sudden death- LVH > 3 cm- Aborted sudden death- Nonsustained VT on Holter

SYNCOPE IN PULMONARYHYPERTENSION

• Usually exertional or immediately post-exercise• “Fixed” right sided obstruction due to

high pulmonary vascular resistance• Inability to increase CO in response to SVR • Decreased cerebral perfusion

SYNCOPE IN SYSTOLIC HEART FAILURE• In patients with syncope, heart failure is

an independent predictor of mortality• Syncopal patients with ICDs have

appropriate therapies delivered • SCD-HeFT:

- Predictors of syncope: QRSd > 120 ms, NYHA III, no beta blocker

- Not predictors: EF, NSVT, AF, other HF Rx- 16% with ICD had syncope; 41% had

appropriate shock (vs 12% with no syncope)- Syncope was predictor of total and CV

mortality, but not sudden death and did not differ among ICD, amio, or placebo pts

- ICDs did not reduce mortality in syncope patients

NEUROCARDIOGENIC (VASOVAGAL) SYNCOPE

• Occurs at all ages• 17 - 35% suffer significant injury• 5 - 7% have fractures• Up to 4% of pts diagnosed with

VVS may have cardiac syncope

FEATURES OF HISTORY IN VVS

• Usually occurs in upright position• Rare during exercise• 3 phases: prodrome, loss of consciousness, postsyncopal period• May have specific triggers:

pain, trauma, stress, “situational” (swallow, micturition, defecation)

• Peri-event amnesia common• Association with chronic fatigue syndrome,

depression, somatic disorders• May run in families• frequency around menses

Male < .001

Age > 54 < .001

Supine NS

Upright NS

Precipitant < .001

No presyncope NS

Warning NS

Diaphoresis < .001

VASOVAGAL vs ARRHYTHMIC* SYNCOPE

*VT + AVBCalkins et alAJM 98:1995

0 20 40 60 80 100

P

VV (%) Arrhythmic (%)

VASOVAGAL vs ARRHYTHMIC* SYNCOPE

Fatigue Post < .001

Confusion NS

Palpitations NS

Incontinence .02

Injury NS

Major Injury NS

Recovery > 0” < .001

0 20 40 60 80 100

P

VV (%) Arrhythmic (%)*VT + AVBCalkins et alAJM 98:1995

NEUROCARDIOGENIC SYNCOPE LV

volume

Venous return

Peripheral venous pooling

HEADUPTILT

Peripheral vasodilation

Hypotension

adrenergic tone

LV contractility

Mechanoreceptor stimulation

(myocardial C fibers)

Vasomotorcenter

Vagal tone

Bradycardia or asytole

* Watch for urinary retention, torsades de pointes VT

VVS: PHARMACOLOGIC THERAPY• Anticholinergic agents

- Disopyramide* (effect vs placebo is controversial)

- Scopolamine• Negative inotropic agents

- Disopyramide*• Fludrocortisone• Vasopressin

• Alpha-adrenergic agonists

- Ephedrine- Etilephrine- Theophylline- Dexedrine- Midodrine

• Serotonin reuptake inhibitors

VVS: PACEMAKER THERAPY

Effect vs placebo is controversial and not supported in RCTs

- Dual chamber

- Rate-drop response or other algorithm which detects heart rate, then tachypaces while periodically searching for spontaneous rhythm

VVS: PACING vs -BLOCKADE (SYDIT)%

syn

cop

e fr

ee p

ts 1.0

0.9

0.8

0.7

0.6

Ammirati et al Circulation 2001; 104:52 N = 93

0 200 400 600 800 1000 Days

Pacemaker

Atenolol

P = 0.0031

“ORTHOSTATIC TRAINING” FOR REFRACTORY NEUROCARDIOGENIC

SYNCOPE

N = 47, mean age 165 in hospital training sessions40 min BID standing against wall at home

Results: (FU 18 ± 5 mos)96% had – HUT (Control 26%)

0% had syncope (Control 57%)

Girolamo et al Circulation 1999;100:1798

LEG CROSSING AND MUSCLE TENSING TO ABORT / MITIGATE VASOVAGAL SYNCOPE•N = 21•At onset of sx, leg crossing with tensing of

abdominal, leg and buttock muscles•BP and HR stabilized in all pts in 3 - 6"•5 / 20 aborted syncope •15 / 20 had delayed onset of syncope

by 0.5 - 11'•At 10 mo FU, 16 / 19 benefited from maneuver•Similar benefit for cardiac pacing

Krediet at al, Circulation 2002;106:1684

ISOMETRIC ARM EXERCISE TO ABORT VASOVAGAL SYNCOPEControl 2 min handgrip

Brignole et al JACC 2002;40:2053 N = 19

Asx 11%Syncope 47%

Asx 63%Syncope 5%

HR112906845

BP178156133111896744

FALLS: SCOPE OF THE PROBLEM

•30% of pts > 65 fall / yr•60% of pts in long-term care facilities fall / yr•10 - 20% result in injury•2 - 6% result in fractures•Usually unwitnessed•30% have LOC with CSM; 80% had amnesia

Kenny et al SAFEPACE JACC 2001;38 N = 175

SAFE-PACE TRIAL**Syncope and Falls in the Elderly

Pacing and Carotid Sinus Evaluation

•Prospective randomized, controlled trial of 175 patients > 50 y.o. with cardioinhibitory carotid sinus hypersensitivity and unexplained falls•Randomized to pacing (with rate-drop response) vs. no pacing•Follow-up one year•Odds-ratio of falls in nonpaced patients 4:1, 0. 35 in paced patients

Kenny et al JACC 2001;38

DDD PACING FOR CAROTID SINUS SYNDROME WITH FALLS, DIZZINESS AND SYNCOPE

Crilley et al Postgrad Med J 73:1997 N = 42

100

80

60

40

20

0Syncope Falls Dizziness

Before After

SYNCOPE WORKUP

• ECG• Holter (overall yield 2-35%)• Event Monitor (patient cannot be syncopal)• Head-up tilt table testing• Electrophysiologic study

(predictive value variable)• Implantable loop recorder

TILT-TABLE TESTING FOR EVALUATION OF SYNCOPE:

SUMMARY OF PRINCIPAL INDICATIONS

Tilt-table testing warranted

• Recurrent syncope or single syncopal episode in a high risk patient, whether or not the medical history is suggestive of

neurally mediated (vasovagal) origin and:

1. No evidence of structural cardiovascular disease, or

2. Structural cardiovascular disease is present, but other causes of syncope have been excluded by appropriate testing

Benditt et al JACC July 1996

Tilt-table testing warranted

• Further evaluation of patients in whom an apparent cause has been established (e.g., asystole, atrioventricular block), but in whom demonstration of susceptibility to neurally mediated syncope would affect treatment plans

• Part of the evaluation of exercise-induced or exercise-associated syncope

Reasonable differences of opinion exist regarding utility of tilt-table testing

• Differentiating convulsive syncope from seizures

• Evaluating patients (especially the elderly) with recurrent unexplained falls

• Assessing recurrent dizziness or presyncope• Evaluating unexplained syncope in the

setting of peripheral neuropathies or dysautonomias

• Follow-up evaluation to assess therapy of neurally mediated syncope

Tilt-table testing not warranted

• Single syncopal episode, without injury and not in a high risk setting, with clear-cut vasovagal features

• Syncope in which an alternative specific cause has been established and in which additional demonstration of a neurally mediated susceptibility would not alter Rx

DIAGNOSTIC YIELD OF AMBULATORY ELECTROCARDIOGRAPHIC MONITORING

(AECG) IN SYMPTOMATIC PATIENTS Sx w/o AECG No Sx with AECG

arrhythmia (%) arrhythmia (%) No. + – + –Zeldis 37 13 34 30 23Clark 98 3 39 41 17Jonas 358 4 0 16 80Kala 108 7 7 16 69Gibson 1,512 2 15 10 79Boudoulas 119 26 13 27 34Diamond 85 44 20 4 33

TOTAL 2,651 21 48Overall yield 2%

DiMarco and Philbrick, Ann Intern Med 6/90

PATIENT PRESENTING WITH SYNCOPE AND SEIZURE

ADVANTAGES AND LIMITATIONS OF IMPLANTABLE LOOP RECORDERS

Advantages

• Prolonged ECG recording capability (to 2 yrs)• Memory - allows activation after syncopal event• Automatic recording, allowing automatic

acquisition of ECG events which fall outside programmable boundaries

• Elimination of technical factors which impair good quality surface ECG recording during sx

• High sx-ECG correlation yield: Dx made in 25-50% of pts, and suggested in an additional 15-25%

Benditt et al

ADVANTAGES AND LIMITATIONS OF IMPLANTABLE LOOP RECORDERS

Limitations• Surgical implantation • Does not record other potentially important

parameters (e.g., BP)• Sx - ECG correlation not available when

automatic recordings are obtained• Does not distinguish vasovagal episodes

from conduction system disease

Benditt et al

RECOMMENDATIONS FOR IMPLANTABLE CARDIOVERTER DEFIBRILLATORS

IN SYNCOPAL PATIENTSClass I

Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at EPS

Class IIaReasonable for patients with unexplainedsyncope, significant LV dysfunction, andnonischemic dilated cardiomyopathy

Reasonable for patients with Brugada syndrome who have had syncope.

ACC/AHA/HRS Guidelines 2008

ACC/AHA/ESC 2006Management of Patients with Ventricular

Arrhythmias and the Prevention of Sudden Cardiac Death

EP Testing in Patients with Syncope

Class IPatients with syncope of unknown cause with impaired LV function or structural heart disease

Class IIa Can be useful in patients with syncope whenbrady- or tachyarrhythmias are suspected,and in whom noninvasive diagnostic studiesare not conclusive.

RECOMMENDATIONS FOR ICDS IN SYNCOPAL PATIENTS

Class IIb

May be consideered in patients with syncope and advanced structural heart disease in whom thorough invasive andnoninvasive investigations have failed to define a cause.

Class III

Syncope of undetermined cause in a patientwithout inducible ventricular tachyarrhythmiasand without structural heart disease.

ACC/AHA/HRS Guidelines 2008

ESC GUIDELINES ON SYNCOPE

For Dx: Strongly recommended

• Suspected or known significant heart disease

• ECG abnormalities suggestive of arrhythmic syncope

• Syncope during exercise

• Syncope causing severe injury

• Strong family history of sudden death

Europace 2004;6: 467-537

Hospital Admission for Syncope Management

ESC GUIDELINES ON SYNCOPE

May need to be admitted• Patients with or without heart disease but with:

Sudden palpitations shortly before syncopeSyncope in supine positionWorrisome family historySignificant physical injury

• Patients with minimal or mild heart disease when there is high suspicion for cardiac syncope

• Suspected pacemaker or ICD problem

Europace 2004;6: 467-537

For Rx:

• Cardiac arrhythmias as cause

• Syncope due to cardiac ischemia

• Syncope due to structural cardiac or pulmonary disease

• Stroke or focal neurologic disorders

• Cardioinhibitory neurally mediated syncope when pacemaker implant is planned

Europace 2004;6: 467 - 537

Hospital Admission for Syncope Management

ESC GUIDELINES ON SYNCOPE

INDICATIONS TO REFER SYNCOPAL PTTO ELECTROPHYSIOLOGIST

•Neurocardiogenic syncope, especially if refractory to avoidance of triggers and drug Rx, or associated with prolonged pauses in cardiac rhythm

•Arrhythmia identified during evaluation:- VT due to any cause - Bradyarrhythmia caused by Rx that

cannot be withheld or changed- Supraventricular tachycardia, esp. with

WPW conduction

INDICATIONS TO REFER SYNCOPAL PT TO ELECTROPHYSIOLOGIST

• Congenital long QT syndrome• Brugada syndrome• Structural heart disease• Syncope in athletes• Syncope during exercise• Short QT syndrome• Origin of syncope remains unknown and

prolonged arrhythmia monitoring by implantable loop recorder is being considered