Syncope UHN/MSH AIMGP Seminar 2007 Yash Patel The only difference between syncope and sudden death is that in one you wake up. 1 1 Engel GL. Psychologic.

SyncopeSyncope

UHN/MSH AIMGP SeminarUHN/MSH AIMGP Seminar

20072007

Yash PatelYash Patel

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.

ReferencesReferences

Neurocardiogenic SyncopeNeurocardiogenic Syncope. . New England Journal New England Journal of Medicineof Medicine 10 March 2005. 352(10): 1004-1010. 10 March 2005. 352(10): 1004-1010. Guidelines on Management of Syncope – Update Guidelines on Management of Syncope – Update 20042004. . European Heart Journal European Heart Journal 25: 2054-2072.25: 2054-2072.Vasovagal SyncopeVasovagal Syncope. . Ann Intern MedAnn Intern Med Nov 7 2002; Nov 7 2002; 133(9):714-725.133(9):714-725.

Incidence and Prognosis of Syncope.Incidence and Prognosis of Syncope. NEJMNEJM 347(12):878-85. Sept 2002.347(12):878-85. Sept 2002.

Primary Care:Primary Care: Syncope.Syncope. NEJMNEJM 343(25):1856-1862. 343(25):1856-1862. Dec 2000. Dec 2000.AHA Statement on Evaluation of SyncopeAHA Statement on Evaluation of Syncope. . CirculationCirculation 113:316-327. Jan 2006. 113:316-327. Jan 2006.

OutlineOutline

1. Objectives1. Objectives

2. Definitions2. Definitions

3. Differential diagnosis3. Differential diagnosis

4. Approach4. Approach

5. Treatment5. Treatment

6. Extra material6. Extra material

ObjectivesObjectives

Learn to distinguish syncope from other Learn to distinguish syncope from other “non-syncopal” conditions that lead to “non-syncopal” conditions that lead to transient loss of consciousnesstransient loss of consciousness

Develop an approach to the assessment Develop an approach to the assessment of patients with syncopeof patients with syncope

How to risk stratify patients with syncopeHow to risk stratify patients with syncope

When to hospitalize patients with syncopeWhen to hospitalize patients with syncope

Case 1Case 1

35 Woman 35 Woman Unwitnessed loss of consciousness (1st. Unwitnessed loss of consciousness (1st. Event)Event)No palpitations or preceding symptomsNo palpitations or preceding symptomsPMHPMH: Hypothyroidism on replacement: Hypothyroidism on replacementExam normalExam normalNo sequelaeNo sequelaeNo injuriesNo injuries

IS THIS SYNCOPE?IS THIS SYNCOPE?WHAT IS SYNCOPE?WHAT IS SYNCOPE?

Some DefinitionsSome Definitions

SyncopeSyncope: sudden, transient loss of : sudden, transient loss of consciousness and postural tone with consciousness and postural tone with spontaneous recovery without therapeutic spontaneous recovery without therapeutic intervention intervention

PresyncopePresyncope: no actual loss of consciousness: no actual loss of consciousness

VertigoVertigo: Dizziness accompanied by a sense : Dizziness accompanied by a sense of motionof motion

Drop attacksDrop attacks: spontaneous falls while : spontaneous falls while standing or walking standing or walking without LOCwithout LOC

Is it Syncope or Seizure?Is it Syncope or Seizure?

Syncope:Syncope:– PrecipitantPrecipitant: pain, : pain,

exercise, micturition, exercise, micturition, defecation, anxietydefecation, anxiety

– PrecedingPreceding sx: sx: sweating and sweating and nauseanausea

– EventEvent: LOC usually : LOC usually <5 min<5 min

– FollowedFollowed by: prompt by: prompt recoveryrecovery

Seizure:Seizure:– PrecedingPreceding sx: aura, sx: aura,

jacksonian marchjacksonian march– EventEvent: clonic or : clonic or

myoclinic jerks, LOC >5 myoclinic jerks, LOC >5 min, incontinencemin, incontinence

– FollowedFollowed by: slowness, by: slowness, neurological deficits, neurological deficits, postictal paresispostictal paresis

Epidemiology of SyncopeEpidemiology of Syncope

Population based incidence Population based incidence (Framingham)(Framingham)::

Men Men 3% per yr.3% per yr.

Women Women 3.5% per yr.3.5% per yr.

It increases with ageIt increases with age::

35 - 44 y/o35 - 44 y/o 0.7% per yr.0.7% per yr.

> 75 y/o> 75 y/o 6% per yr.6% per yr.

Case 1Case 1

35 Woman Unwitnessed loss of consciousness (1st. Event)No palpitations or preceding symptomsPMH: Hypothyroidism on replacementExam normalNo sequelaeNo injuries

IS THIS SYNCOPE?YES, THIS WAS PROBABLY A SYNCOPAL YES, THIS WAS PROBABLY A SYNCOPAL

EVENTEVENT

REMEMBER SYNCOPE IS A REMEMBER SYNCOPE IS A SYMPTOMSYMPTOM NOT NOT A DIAGNOSISA DIAGNOSIS

Case 2Case 2

70 Woman70 Woman

PMHPMH: CAD - : CAD - Previous MIPrevious MI

CABG x 3 10 yr. AgoCABG x 3 10 yr. Ago

MedsMeds: Metoprolol, ASA, Fosinopril, recently : Metoprolol, ASA, Fosinopril, recently started on clarithromycin for CAPstarted on clarithromycin for CAP

Witnessed syncope lasting 15 sec.Witnessed syncope lasting 15 sec.

Palpitations prior to eventPalpitations prior to event

ECG: Inferior Q waves, no arrhythmiasECG: Inferior Q waves, no arrhythmias

WHAT IS THE CAUSE OF HER SYNCOPE?WHAT IS THE CAUSE OF HER SYNCOPE?

Syncope: Etiology

OrthostaticCardiac

Arrhythmia

StructuralCardio-

Pulmonary

*

1• Vasovagal• Carotid

Sinus• Situational

CoughPost- micturition

2• Drug Induced• ANS

FailurePrimarySecondary

3• Brady

Sick sinusAV block

• TachyVTSVT

• Long QT Syndrome

4 • Aortic

Stenosis• HOCM• PulmonaryHypertension

5• Psychogenic• Metabolic

e.g. hyper-ventilation

• Neurological

Non-Cardio-

vascularNeurally-Mediated

Unknown Cause = 34%

24% 11% 14% 4% 12%

Case 2Case 2

70 Woman70 Woman

PMHPMH: CAD - : CAD - Previous MIPrevious MI

CABG x 3 10 yr. AgoCABG x 3 10 yr. Ago

MedsMeds: Metoprolol, ASA, Fosinopril, recently started on clarithromycin for CAP: Metoprolol, ASA, Fosinopril, recently started on clarithromycin for CAP

Witnessed syncope lasting 15 sec.Witnessed syncope lasting 15 sec.

Palpitations prior to eventPalpitations prior to event

ECG: Inferior Q waves, no arrhythmiasECG: Inferior Q waves, no arrhythmias

WHAT IS THE APPROACH TO EVALUATING WHAT IS THE APPROACH TO EVALUATING SOMEONE WITH SYNCOPE?SOMEONE WITH SYNCOPE?

ApproachApproach

1. 1. HxHx, , PhysicalPhysical and and ECGECG form core workup form core workup (yields diagnosis in ~ 50 % of cases) (yields diagnosis in ~ 50 % of cases)

2. Cardiac causes carry a worse prognosis and 2. Cardiac causes carry a worse prognosis and should be excluded firstshould be excluded first

3. Exertional syncope or existing heart disease 3. Exertional syncope or existing heart disease predicts worse outcomes and warrants more predicts worse outcomes and warrants more intense investigationintense investigation

4. In the elderly think of polypharmacy4. In the elderly think of polypharmacy

HistoryHistory: focus on...: focus on...

Precipitating FactorsPrecipitating Factors– exertion, position, neck or arm movement, specific activities exertion, position, neck or arm movement, specific activities

(urination, defecation) and stressful situations(urination, defecation) and stressful situations

Associated Symptoms:Associated Symptoms:– Nausea, diaphoresis, blurred vision - vasovagalNausea, diaphoresis, blurred vision - vasovagal– Diarrhea, Vx, GI bleed - volume contractionDiarrhea, Vx, GI bleed - volume contraction– Prodromal aura, incontinence - seizureProdromal aura, incontinence - seizure

Medications: Medications: – side effects, overdose, interactionsside effects, overdose, interactions– antiHTN, Digoxin, diuretics, antibiotics antiHTN, Digoxin, diuretics, antibiotics

Family Hx: Family Hx: Long QT, WPW, HOCM, CAD, Brugada Long QT, WPW, HOCM, CAD, Brugada SyndromeSyndrome

Physical ExamPhysical Exam: focus on...: focus on...

Vitals: Orthostatic, BP in both armsVitals: Orthostatic, BP in both arms

CSM (avoid if carotid bruits present)CSM (avoid if carotid bruits present)

Cardiac examCardiac exam

Neurologic examNeurologic exam

Misc: Pulses, bruits, OB in stoolMisc: Pulses, bruits, OB in stool

Case 2Case 2

70 Woman70 Woman

PMHPMH: CAD - : CAD - Previous MIPrevious MI

CABG x 3 10 yr. AgoCABG x 3 10 yr. Ago

MedsMeds: Metoprolol, ASA, Fosinopril, recently started on clarithromycin for CAP: Metoprolol, ASA, Fosinopril, recently started on clarithromycin for CAP

Witnessed syncope lasting 15 sec.Witnessed syncope lasting 15 sec.

Palpitations prior to eventPalpitations prior to event

ECG: Inferior Q waves, no arrhythmiasECG: Inferior Q waves, no arrhythmias

SHOULD SHE BE ADMITTED TO HOSPITAL?SHOULD SHE BE ADMITTED TO HOSPITAL?

WHAT INVESTIGATIONS ARE INDICATED?WHAT INVESTIGATIONS ARE INDICATED?

When to Hospitalize?When to Hospitalize?

1. For Investigation:1. For Investigation:structural heart disease, arrhythmias or structural heart disease, arrhythmias or

ischemia (palpitations or chest pain), or ischemia (palpitations or chest pain), or abnormal ECGabnormal ECG

2. For Treatment:2. For Treatment:

obstructive HD, severe orthostasis, or obstructive HD, severe orthostasis, or adverse drug reactionsadverse drug reactions

3. Consider in all patients with injury 3. Consider in all patients with injury following syncopefollowing syncope

Investigations for Suspected Investigations for Suspected Cardiac SyncopeCardiac Syncope

Guided by history, physical and clinical suspicion Guided by history, physical and clinical suspicion (ie/risk factors, age >60)(ie/risk factors, age >60)Echo - abnormalities found in 5-10 % but these Echo - abnormalities found in 5-10 % but these may not relate to sxmay not relate to sxStress testing if ischemic arrhythmia suspectedStress testing if ischemic arrhythmia suspectedProlonged ECG recording Prolonged ECG recording Electrophysiologic testingElectrophysiologic testingIf above testing is negative and syncope If above testing is negative and syncope recurrent, evaluate for neurally mediated recurrent, evaluate for neurally mediated syncopesyncope

ECGECG Features Suggesting Features Suggesting Arrhythmic EtiologyArrhythmic Etiology

Bifasicular blockBifasicular blockIntraventricular conduction abn (QRS>.12)Intraventricular conduction abn (QRS>.12)Mobitz II AV blockMobitz II AV blockSinus brady, sinus block or sinus pause >3 sec in Sinus brady, sinus block or sinus pause >3 sec in absence of negative chronotropesabsence of negative chronotropesPre-excited QRSPre-excited QRSProlonged QTProlonged QTBrugada Syndrome:RBBB and ST elevation V1-V3Brugada Syndrome:RBBB and ST elevation V1-V3Neg T waves in R precordial leads, epsilon waves and Neg T waves in R precordial leads, epsilon waves and ventricular late potentials (ARVD)ventricular late potentials (ARVD)Q wavesQ waves

Electrocardiographic MonitoringElectrocardiographic Monitoring

“ “ECG monitoring is unlikely to be helpful in ECG monitoring is unlikely to be helpful in patients who do not have clinical or ECG patients who do not have clinical or ECG features suggestion an arrhythmic features suggestion an arrhythmic syncope and therefore should not be syncope and therefore should not be performed”performed”

Electrocardiographic MonitoringElectrocardiographic Monitoring

In hospital monitoring if high riskIn hospital monitoring if high risk

Holter monitoring Holter monitoring – True + (arrhythmias with sx) ~ 4% of testsTrue + (arrhythmias with sx) ~ 4% of tests– True - (sx with no arrhythmia) ~ 17% of True - (sx with no arrhythmia) ~ 17% of

teststests

Loop recording for longer monitoringLoop recording for longer monitoring– External if inter-symptom interval <4 wksExternal if inter-symptom interval <4 wks

Consider EPS in anyone with structural heart Consider EPS in anyone with structural heart disease with a non-diagnostic Holterdisease with a non-diagnostic Holter

Case 3Case 3

82 Man 82 Man

PMHPMH: HTN, BPH, Glaucoma, COPD, Depression: HTN, BPH, Glaucoma, COPD, Depression

MedsMeds: Diltiazem, ASA, Salbutamol, Ipratropium, : Diltiazem, ASA, Salbutamol, Ipratropium, Prazosin, Paroxetine, Tyl #3, OmeprazolePrazosin, Paroxetine, Tyl #3, Omeprazole

Syncope while urinating in early AM, shortly after Syncope while urinating in early AM, shortly after risingrising

Trauma to forehead from episodeTrauma to forehead from episode

YOUR DIAGNOSIS IS NEURALLY-MEDIATED YOUR DIAGNOSIS IS NEURALLY-MEDIATED SITUATIONAL SYNCOPESITUATIONAL SYNCOPE

WHAT INVESTIGATIONS DOES HE NEED?WHAT INVESTIGATIONS DOES HE NEED?

Investigations for Suspected Investigations for Suspected Neurally Mediated SyncopeNeurally Mediated Syncope

The majority of patient with single or rare The majority of patient with single or rare episodes do not require confirmatory testsepisodes do not require confirmatory testsInvestigations in patients Investigations in patients withoutwithout suspected heart disease and suspected heart disease and recurrent or recurrent or severe syncope:severe syncope:– Tilt testingTilt testing– Carotid massageCarotid massage– Prolonged ECG monitoringProlonged ECG monitoring

Case 135 Woman Unwitnessed loss of consciousness (1st. Event)No palpitations or preceding symptomsPMH: Hypothyroidism on replacementExam normalNo sequelaeNo injuries

Case 2Case 270 Woman70 WomanPMHPMH: CAD - Previous MI : CAD - Previous MI CABG x 3 10 yr. AgoCABG x 3 10 yr. AgoMedsMeds: Metoprolol, ASA, : Metoprolol, ASA, Fosinopril, recently started Fosinopril, recently started on clarithromycin for CAPon clarithromycin for CAPWitnessed syncope lasting Witnessed syncope lasting 15s15sPalpitations prior to eventPalpitations prior to eventECG: Inferior Q waves, no ECG: Inferior Q waves, no arrhythmiasarrhythmias

Case 3Case 382 Man 82 Man PMHPMH: HTN, BPH, : HTN, BPH, Glaucoma, COPD, Glaucoma, COPD, DepressionDepressionMedsMeds: Diltiazem, ASA, : Diltiazem, ASA, Salbutamol, Ipratropium, Salbutamol, Ipratropium, Prazosin, Paroxetine, Tyl Prazosin, Paroxetine, Tyl #3, Omeprazole#3, OmeprazoleSyncope while urinating Syncope while urinating in early AM, shortly after in early AM, shortly after risingrisingTrauma to forehead from Trauma to forehead from episodeepisode

WHAT IS THE PROGNOSIS FOR EACH OF THESE PATIENTS WITH SYNCOPE?

Risk Stratification and Prognosis in Risk Stratification and Prognosis in SyncopeSyncope

Structural heart disease is the most Structural heart disease is the most important predictor of mortality and important predictor of mortality and sudden death in patients with syncopesudden death in patients with syncopePoor PrognosisPoor Prognosis

Structural heart diseaseStructural heart disease

Excellent PrognosisExcellent PrognosisYoung, healthy, normal ECGYoung, healthy, normal ECGNeurally-mediated syncopeNeurally-mediated syncopeOrthostatic hypotensionOrthostatic hypotensionUnexplained syncopeUnexplained syncope

Prognosis in SyncopePrognosis in Syncope(from Framingham database)(from Framingham database)

EtiologyEtiology Total MortalityTotal Mortality

1yr1yr 5yr5yr

CardiacCardiac 15%15% 40%40%

NoncardiacNoncardiacNeurologicNeurologic 5%5% 30%30%

Vasovagal/OthersVasovagal/Others 2%2% 15%15%

UnknownUnknown 5%5% 25%25%

Controls w/o syncopeControls w/o syncope 2%2% 15%15%

NEJM 2002;347:878NEJM 2002;347:878

SummarySummary

Syncope is a common symptomSyncope is a common symptom

History/Physical can establish a diagnosis History/Physical can establish a diagnosis in 50% of casesin 50% of cases

The approach involves risk assessment for The approach involves risk assessment for the presence of cardiac diseasethe presence of cardiac disease

Investigations and Treatment are tailored Investigations and Treatment are tailored to the suspected etiologic cause of to the suspected etiologic cause of syncopesyncope

Extras...Extras...

Driving after syncopeDriving after syncope

Treatment of syncopeTreatment of syncope

Mechanism of Vasovagal syncopeMechanism of Vasovagal syncope

Tilt-table testingTilt-table testing

Neurologic evaluationNeurologic evaluation

Psychiatric evaluationPsychiatric evaluation

Driving and SyncopeDriving and Syncope

Driving and SyncopeDriving and Syncope

Physicians are obliged to disclose risk of Physicians are obliged to disclose risk of driving to patients and advise them not to driving to patients and advise them not to drivedrive

7 provinces (including Ontario) and all 7 provinces (including Ontario) and all territories have mandatory reporting territories have mandatory reporting legislationlegislation

PrivatePrivate CommercialCommercialSingle episode of Single episode of vasovagalvasovagal

No restrictionNo restriction No restrictionNo restriction

Dx and tx cause Dx and tx cause (ie/ PPM)(ie/ PPM)

Wait 1 weekWait 1 week Wait 1 monthWait 1 month

Reversible cause Reversible cause (ie/ hemorrhage)(ie/ hemorrhage)

No restriction No restriction No restrictionNo restriction

Situational Situational w/avoidable w/avoidable triggertrigger

Wait 1 week Wait 1 week Wait 1 weekWait 1 week

UnexplainedUnexplained

Single episodeSingle episode

RecurrentRecurrent

Wait 1 weekWait 1 week

Wait 3 monthsWait 3 months

Wait 12 monthsWait 12 months

Wait 12 monthsWait 12 months

Recurrent Recurrent Vasovagal Vasovagal

Wait 1 weekWait 1 week Wait 12 monthsWait 12 months

Syncope and DrivingSyncope and Driving

Further guidelines exist for patients with Further guidelines exist for patients with arrhythmia, MI, valvular heart disease and arrhythmia, MI, valvular heart disease and devicesdevices

See CCS Consensus Conference 2003: See CCS Consensus Conference 2003: Assessment of Cardiac Patients for Assessment of Cardiac Patients for Fitness to Drive and Fly. Fitness to Drive and Fly. Canadian Canadian Journal of CardiologyJournal of Cardiology, 2004, 20(13): , 2004, 20(13): 1313-1323.1313-1323.

Treatment of SyncopeTreatment of Syncope

TreatmentTreatment

Identifiable arrhythmia, structural heart Identifiable arrhythmia, structural heart disease, or non-syncopal event: disease, or non-syncopal event: Rx Rx accordinglyaccordingly

Treatment: Neurally-MediatedTreatment: Neurally-Mediated

Education and reassurance usually Education and reassurance usually sufficientsufficientAdditional treatment may be warranted if:Additional treatment may be warranted if:– Very frequentVery frequent– Unpredictable and exposes pts to traumaUnpredictable and exposes pts to trauma

It may be valuable to assess the relative It may be valuable to assess the relative contribution of cardioinhibition and contribution of cardioinhibition and vasodepressionvasodepression

Treatment: NonpharmacologicTreatment: Nonpharmacologic

Avoid trigger eventsAvoid trigger events

Modify or discontinue hypotensive drugsModify or discontinue hypotensive drugs

OtherOther– Increase fluid intake (2L water/day)Increase fluid intake (2L water/day)– Salt supplementsSalt supplements– Isometric leg and arm counter-pressure maneuversIsometric leg and arm counter-pressure maneuvers– Tilt trainingTilt training– Compression StockingsCompression Stockings

Treatment: DrugsTreatment: Drugs

Beta-blockers discouraged in 2004 ESC Beta-blockers discouraged in 2004 ESC guidelinesguidelines

Other meds with Other meds with limitedlimited evidence: evidence:– FludricortisoneFludricortisone– MidodrineMidodrine– SSRIsSSRIs– OthersOthers

Treatment: DevicesTreatment: Devices

Permanent dual chamber pacing may Permanent dual chamber pacing may have a role in:have a role in:– Those with no prodromeThose with no prodrome– Failure of other therapiesFailure of other therapies– Profound bradycardia or asystole during Profound bradycardia or asystole during

syncope syncope >5 attacks per year>5 attacks per year

Age >40Age >40

Mechanism of Vasovagal SyncopeMechanism of Vasovagal Syncope

Mechanism of Vasovagal Mechanism of Vasovagal SyncopeSyncope

Bezold–Jarisch ReflexBezold–Jarisch Reflex: Excessive venous : Excessive venous pooling triggers a chain of events that pooling triggers a chain of events that culminates in vasodilatation and culminates in vasodilatation and bradycardia (instead of the physiologic bradycardia (instead of the physiologic compensatory responses of compensatory responses of vasoconstriction and tachycardia)vasoconstriction and tachycardia)

This in turn leads to the hypotension and This in turn leads to the hypotension and loss of consciousness associated with loss of consciousness associated with vasovagal syncope.vasovagal syncope.

Common Triggers in Situational Common Triggers in Situational SyncopeSyncope

DefecationDefecation

Micturition (especially in elderly men with BPH that Micturition (especially in elderly men with BPH that wake up at night and strain to pass urine)wake up at night and strain to pass urine)

Heavy straining Heavy straining

CoughCough

All situations that induce valsalva => All situations that induce valsalva => – decreased preload + decreased preload + – cardioinhibitory and vasodepressor reflexes cardioinhibitory and vasodepressor reflexes

produced by central baroreceptorsproduced by central baroreceptors

Tilt-Table TestingTilt-Table Testing

Vasovagal SyncopeVasovagal Syncope

Test = Head Up Tilt-table Test = Head Up Tilt-table testing using a provocative testing using a provocative agent (Isoproterenol or agent (Isoproterenol or Nitroglycerin):Nitroglycerin):

Sn and Sp difficult to Sn and Sp difficult to evaluate because of lack of evaluate because of lack of gold standardgold standardACC has guidelines on ACC has guidelines on testing (JACC 1996:28 pg testing (JACC 1996:28 pg 263-275)263-275)

Head-up Tilt table testingHead-up Tilt table testing

Indicated in:Indicated in:

1. Recurrent syncope1. Recurrent syncope

2. Single syncopal event 2. Single syncopal event resulting in injury or resulting in injury or occurring in high risk occurring in high risk settingsetting

3. Where the treatment of 3. Where the treatment of syncope may be syncope may be complicated by vasovagal complicated by vasovagal symptomssymptoms

Contraindicated inContraindicated in presence of obstructive presence of obstructive heart disease or heart disease or cerebrovascular stenosiscerebrovascular stenosis

Neurologic and Psychiatric TestingNeurologic and Psychiatric Testing

Neurologic TestingNeurologic Testing

Low yield:Low yield:– EEG ~ 2%EEG ~ 2%– CT head ~ 4%CT head ~ 4%– Doppler carotids (no studies)Doppler carotids (no studies)

The majority of positives can be identified The majority of positives can be identified by history: e.g. seizure eventsby history: e.g. seizure events

Bottom line: only indicated if suspicion of Bottom line: only indicated if suspicion of seizure or neuro deficits presentseizure or neuro deficits present

Psychiatric evaluationPsychiatric evaluation

Syncope can be a feature of:Syncope can be a feature of:– Anxiety disorders: Gen anxiety or panicAnxiety disorders: Gen anxiety or panic– SomatizationSomatization– Substance abuseSubstance abuse

These tend to occur recurrently in younger These tend to occur recurrently in younger patients without heart diseasepatients without heart disease

In elderly patients organic (i.e. cardiac) In elderly patients organic (i.e. cardiac) causes must be excludedcauses must be excluded