syncope intvestigations

7/28/2019 Syncope Intvestigations

1/12

Seizure (2004) 13, 537548

The investigation of syncope

Savvas Hadjikoutis a, Peter OCallaghan b, Philip E.M. Smith a,*

aThe Welsh Epilepsy Unit, Department of Neurology, University Hospital of Wales, Heath Park, Cardiff

CF14 4XW, UKb

Department of Cardiology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK

KEYWORDS

Syncope;

Investigations;

Tilt table test;

Electrocardiograph;

Carotid sinus massage;

Echocardiography;

EP studies

Summary Patients with syncope are usually referred to either neurology or cardiologyclinics, yet the facilities for detailed syncope investigation are mostly in cardiac units.The diagnosis rests principally upon the history, but investigations may be requiredto support the clinical diagnosis. Close collaboration between the epilepsy clinicianand a cardiologist is essential for effective investigation and safe management ofsyncope. It is frequently misdiagnosed and often erroneously treated as epilepsy.Furthermore, it is potentially a marker of sudden death when associated with certaincardiac disorders. Here we review the main syncope types and explore diagnosticapproaches. 2004 BEA Trading Ltd. Published by Elsevier Ltd. All rights reserved.

Introduction

Syncope is an abrupt and transient loss of conscious-ness associated with loss of postural tone that fol-lows a sudden fall in cerebral perfusion. Recurrentsyncope is commoner than epilepsy (syncope preva-lence 337%;1,2 epilepsy prevalence 0.5%3) and ac-counts for 3% of emergency department visits and1% of hospital admissions.4 Recent work has shownthat syncope is often misdiagnosed and erroneouslytreated as epilepsy.5 The diagnosis rests princi-

pally upon the history, but investigations may berequired to support the clinical diagnosis. Becausethe range of underlying causes of syncope is wide,the physicians first task is to distinguish betweenthe usually benign, e.g. vasovagal syncope, and thepotentially life threatening, e.g. cardiac syncope.

Neurologists may have limited access to the rangeof cardiac investigations that may be necessary to

*Corresponding author. Tel.: +44-29-207-42834;fax: +44-29-207-66144.

E-mail address: [email protected] (P.E.M. Smith).

clarify the cause and treatment of syncope. Closecollaboration between the epilepsy clinician anda cardiologist is essential for safe management ofthese patients.

Syncope types

The main causes of syncope are shown in Table 1.In approximately one-third of cases, a presumptivediagnosis can be made on the basis of the clinical

history, physical examination and 12 lead electro-cardiogram (ECG). The diagnosis is undeterminedin two-thirds of cases, termed syncope of undeter-mined origin (SUO). Even after detailed investiga-tion, the cause remains unexplained in a one-thirdof all patients.6

Neurally-mediated (reflex) syncope

Neurally-mediated syncope describes loss of con-sciousness associated with reflex vasodilation andbradycardia occurring as a response to certain

1059-1311/$30 see front matter 2004 BEA Trading Ltd. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.seizure.2003.12.011


2/12

538 S. Hadjikoutis et al.

Table 1 Causes and classification of syncope.

Neurally-mediated reflex syncope Vasovagal syncope Reflex syncope with specific precipitants

Carotid sinus syndromeOther situational, e.g. cough,

micturition, swallowing

Orthostatic syncope (autonomic failure) Primary (e.g. multiple system atrophy) Secondary (diabetes, amyloid, drugs)

Cardiac syncope Tachyarrhythmias

Sustained monomorphic ventricular tachycardiaPolymorphic ventricular tachycardiaSVT with rapid ventricular rate

BradyarrhythmiasImpulse generation (e.g. sinus node diseases)Impulse conduction (e.g. complete heart block)

Mechanical obstructionAortic stenosisHypertrophic cardiomyopathyMitral stenosisAtrial myxoma

Central nervous system syncope Ictal arrhythmia Intermittent obstructive hydrocephalus Transient ischaemic attacks Migraine

Metabolic syncope Hypoglycaemia

Hypocalcaemia

Psychogenic syncope Panic disorder Conversion

Syncope of undetermined origin (SUO)

triggers. Most neurally-mediated reflex syncopecan be categorised as vasovagal syncope, but thereare subgroups where syncope is provoked only byspecific triggers, e.g. coughing or swallowing.

Vasovagal syncopeReflex (vasovagal) syncope is the commonest causeof syncope. It is generally benign and is the usual ex-planation for fainting in otherwise healthy individ-uals of all ages, but especially children and youngadults. A patients vasovagal tendency also influ-ences the likelihood and severity of syncope devel-oping from seemingly unrelated causes, e.g. aorticstenosis and hypertrophic cardiomyopathy. In vaso-vagal syncope, the blood pressure (BP) and heartrate are typically maintained until a sudden haemo-dynamic collapse.

Clinical features. The main clinical features thatdistinguish vasovagal syncope from seizures7 areshown in Table 2.

Situations and triggers. Patients may reportcertain precipitants that suggest the diagnosis.Vasovagal syncope might occur in the bathroom,

at night or in a hot restaurant; specific trig-gers include prolonged standing, hot crowdedenvironments, emotional trauma and pain. Insusceptible individuals, coughing, swallowingor micturition may provoke vasovagal syncope.Exercise-induced vasovagal syncope must be in-vestigated in detail to distinguish it from cardiacsyncope.8

Prodrome. Warning symptoms (presyncope) thatdevelop over 15min include lightheadness, nau-sea, sweating, greying or blacking of vision, muf-fled hearing, and feeling distant.

Index event. During the period of unconscious-ness, a witness may describe pallor, sweating,cold skin, and brief convulsive jerks.9 Inconti-nence and injury are uncommon, and lateraltongue biting rare.

Recovery. Any post-ictal confusion is typicallybrief, usually a few seconds, unless there hadbeen associated head trauma. Although patientswith neurally-mediated syncope are orientatedsoon after recovery, they are typically fatiguedfor minutes to hours afterwards, in contrast topatients with cardiac syncope who recover com-pletely almost immediately on regaining con-sciousness.

Vasovagal syncope with specific triggersCough syncope, micturition syncope, swallow syn-cope, etc. are variants of vasovagal syncope wherecertain specific situations act as powerful triggersto vagal-mediated haemodynamic collapse.

Carotid sinus syndromePatients with carotid sinus syndrome have exag-gerated baroreceptor-mediated reflexes, leadingto symptomatic bradycardia and hypotension. Itis rare below aged 50 years, but is an importantyet frequently overlooked cause of syncope inthe elderly. If is specifically sought, carotid sinussyndrome is diagnosed in about 14% of elderly pa-tients presenting with suspected presyncope orsyncope.10 Carotid sinus hypersensitivity (carotidsinus massage resulting in 3 s asystole) is a commonfinding in elderly individuals and, in general, moremalignant causes of syncope (e.g. scar-relatedventricular tachycardia) should be consideredbefore a diagnosis of carotid sinus syndrome ismade.


3/12

The investigation of syncope 539

Table 2 Clinical distinction of neurally-mediated reflex (vasovagal) syncope seizures and cardiac syncope.

Vasovagal syncope Seizure Cardiac syncope

Trigger Common (upright, bathroom,blood, needles)

Rare (flashing lights,hyperventilation)

Rare, exertional (considerleft ventricular outflowobstruction)

Prodrome Almost always (presyncope) Common (aura) Uncommon or brief

Onset Gradual (often minutes) Usually sudden Usually sudden

Duration 130 s 13 min Variable

Convulsive jerks Common (brief) Common (prolonged) Common (brief)

Incontinence Uncommon Common Uncommon

Lateral tongue bite Very rare Common Very rare

Colour Very pale, cold skin Pale or flushed (partialseizure); blue(tonic-clonic seizure)

Very pale, cold skin

Post-ictal confusion Rare (wakes on floor) Common (wakes inambulance) Rare (wakes on the floor)

Recovery Quickly orientated Slow (confused) Quickly orientatedFatigue (minutes-hours) Fatigue (minutes-hours) No fatigue

Clinical features. Carotid sinus syndrome presents,usually in the elderly, with dizziness, syncope orfalls, often with injury. Important precipitating fac-tors include head movements (especially with tightneckwear or neck pathology), prolonged standing,heavy meals, or straining on micturition, defeca-

tion and coughing.

Cardiac syncope

Cardiac syncope results from disorders of eithercardiac rhythm or cardiac structure (Table 1). Dis-orders of cardiac rhythm are the second most com-mon cause of syncope. Tachyarrhythmias or brad-yarrhythmias can result in a sudden precipitousreduction in cardiac output resulting in loss of con-sciousness with little warning. Tachyarrhythmiascan occur in a heterogeneous group of individuals.Patients with significant structural heart disease(e.g. history of prior myocardial infarction) andscar-related ventricular tachycardia are at highrisk of sudden cardiac death due to a cardiac arrest(1020% annual risk). Patients with genetic disor-ders such as congenital long QT syndrome (Fig. 1)or Brugada syndrome (Fig. 2) can present with syn-cope and apparently normal hearts and be at riskof sudden and unexpected death. At the other endof the spectrum are patients with structurally nor-mal hearts and regular forms of supraventriculartachycardia (e.g. AV node-dependent tachycardia)

who may present with syncope rather than palpita-tions. Bradyarrhythmias occur mainly in the elderlydue to degenerative changes (fibrosis) of the sinusnode or the specialised conducting tissue (AV nodeor His-Purkinje tissue). Evidence of conduction sys-tem disease such as complete left bundle branchblock, trifascicular heart block or evidence of sinusnode dysfunction such as pauses alternating withatrial tachyarrhythmias (tachy-brady syndrome)increase the possibility that syncope is due to abradyarrhythmias. Less commonly cardiac syncopecan be caused by mechanical obstruction to eitherleft ventricular outflow (hypertrophic cardiomy-opathy, aortic stenosis) or left ventricular inflow(mitral stenosis, atrial myxoma).

Clinical featuresCardiac syncope can occur from any posture. Thereis usually little warning and recovery is rapid. Fre-quently syncope due to tachyarrhythmias occurswith no perception of palpitations. Syncope shouldalways be considered due to a life-threatening ven-tricular tachyarrhythmia in any patient with priorhistory of myocardial infarction, history of heartfailure, or a family history of sudden, unexpecteddeath at a young age (


4/12


Figure 1 ECG demonstrating long QT syndrome. Note that the QT interval extends from the start of the QRS complexto the end of the T wave, and normally shortens with increased heart rates. The corrected QT interval (QTc) can bederived from the equation QTc = QT/RR interval (normal = 0.46 s in males and 0.47 s in females). This is the ECGfrom a patient with inherited long QT syndrome. The corrected QT interval is 0.61 s. Reproduced with permissionfrom: JAMA 2003;289(16):2042.

either at rest or during low-level activity. Finally,

a detailed drug history should be obtained to as-sess if the patient is on any drug associated withacquired form of long QT syndrome.

Orthostatic syncope

Orthostatic hypotension is where autonomic dys-function impairs the normal vasoconstriction re-sponses to a postural BP fall, allowing a postural fallin systolic BP exceeding 20mmHg within seconds ora few minutes of standing. Orthostatic syncope oc-curs most often in the elderly but may accompanyany autonomic peripheral neuropathy (diabetes,alcohol, amyloidosis) or complex autonomic failure(e.g. multiple system atrophy). Associated dysau-tonomic symptoms include impotence, urinary in-continence, nocturnal diarrhoea and constipation.Certain medications may exacerbate the problem,especially antihypertensives, diuretics, tricyclicantidepressants and anti-Parkinsonian treatment.

Clinical featuresOrthostatic syncope occurs within seconds or min-utes of becoming upright, typically on rising andafter meals. Unlike in vasovagal syncope, the skin

stays warm, the heart rate is unchanged despite the

BP fall, and sweating is absent. Measurements of BPand heart rate both lying and standing are usuallysufficient to confirm the diagnosis.

Central nervous system (CNS) syncope

These are rare causes of syncope.

Clinical features

Seizure-induced arrhythmogenic syncope re-sults from heart rate and rhythm changes duringseizures.11 Tachycardias commonly accompanyseizures, though rarely lead to symptoms.12

Bradyarrhythmias are rarer, usually associatedwith left sided partial seizure onset,13 and leadto loss of consciousness which is syncopal ratherthan primarily due to the seizure.14,15 Such casesare often initially diagnosed as cardiac arrhyth-mogenic syncope, but partial seizures continuewithout collapse following cardiac pacing.

Intermittent obstructive hydrocephalus, e.g.third ventricular cyst or Chiari malformation,typically, though not invariably, present as occip-ital pressure headaches building over seconds


5/12


Figure 2 Precordial leads of an ECG demonstrating theBrugada pattern: persistent ST elevation in the rightventricular precordial leads (V1V3), more evident onV2 (arrow). Reproduced with permission from: JACC2003;41(10):1666.

before loss of consciousness. Colloid cysts of thethird ventricle may present as drop attacks(without loss of consciousness) owing to stretch-ing of the corticospinal fibres supplying the lowerlimbs. Intermittent elevation of intracranialpressure is a potential cause of sudden death.

Transient ischaemic attacks rarely lead to loss ofconsciousness, and then only with involvementof the posterior circulation; there are usually as-sociated brainstem symptoms including vertigo,ataxia, diplopia, and parasthesiae. A history ofhypertension and vascular disease is usual.

Migraine syncope usually manifests as a grad-ual onset loss of consciousness in the context ofother migraine symptoms and is typically associ-ated with familial hemiplegic migraine. Basilarartery migraine presents with syncope (com-monly prolonged), typically preceded by visualblackening, vertigo, or diplopia.

Psychogenic syncope

Psychological disorders may present as syncope.The two main causes are panic (especially withhyperventilation) and dissociative (conversion) dis-orders. Non-epileptic attacks and syncope may also

coexist in the same patient, sometimes prompt-ing aggressive treatment of apparently resistantsyncope.

Clinical features

Panic disorder may cause attacks that culminatein true syncope through hyperventilation-inducedhypocapnia with cerebral vasoconstriction. Facialand limb tingling are typical, and may be lat-eralised. Accompanying symptoms include anx-iety, light-headedness, breathlessness, palpita-

tion, chest and throat tightness, blurred visionand carpopedal spasms.

Dissociative non-epileptic attack disorder (pseu-doseizures) may mimic recurrent syncope. Thecondition is notoriously difficult to diagnose andcarries significant resource implications and po-tential unnecessary morbidity if overlooked. Ma-jor features distinguishing pseudoseizures fromepileptic seizures include prolonged duration,normal colour and breathing (or hyperventila-tion) during attacks, erratic movements, fighting,pelvic thrusting, back arching, crying, and the

absence of tongue biting, self-injury or post-ictalconfusion.

Metabolic syncope

Syncope sometimes results from metabolic dis-turbances. Hypoglycaemia, easily diagnosed andreadily reversed, should be considered in all pa-tients with undiagnosed altered consciousness.Insulin-treated diabetes mellitus is the obviouscause. Insulinoma is rare and frequently missed.Other metabolic disorders, e.g. hypocalcaemia,

may present as pre-syncope and rarely syncope.

Clinical featuresHypoglycaemic syncope presents as recurrentblackouts, often with behaviour disturbance, con-fusion and convulsions. Insulinoma-related neuro-glycopenia occurs especially in sleep and in theearly morning, and are associated with weight gainfrom frequent sweet drinks. Hypocalcaemia (e.g.from hypoparathyroidism) may present as recur-rent episodes of tingling, carpopedal spasm andsyncope.


6/12


SYNCOPE

History, Clinical Examination, ECG

Diagnosis Made SUO Diagnosis Suspected

Echocardiography

Treat Specific tests

Structural heart disease No structural heart disease

*Cardiac evaluation

Diagnostic Non diagnostic Single/rare episode Recurrent or severe

Treat **No further evaluation Tilt table test

***Prolonged ECG monitoring

Psychiatric evaluation

Figure 3 Algorithm for diagnosing syncope (modified from American College of Cardiologists, 1999). In selective

patients should include invasive EP studies. Unless syncope occurred in a high-risk setting, e.g. while driving, orcaused significant injury. Including implantable loop recorder; SUO: syncope of undetermined origin.

Investigations

The clinical history, physical examination, andelectrocardiography (ECG) are essential in theinitial evaluation of a patient with syncope. Af-ter these are completed, about 45% of patientshave a definite diagnosis, and a further 8% havea presumptive diagnosis that can be confirmedby directed testing.2 Such is the diversity of un-derlying causes of syncope, however, that theinvestigations must be selected from a broadrange of possible tests. Fig. 3 gives an algorithmoutlining suggested investigation pathways (mod-ified from the American College of Cardiology,199916,17).

Clinical history

A history taken by an appropriately experiencedclinician, and including a witness account, is usuallysufficient to secure a diagnosis without the need

for detailed investigations. The history should focuson precipitants of the episode (situation and trig-gers), the premonitory symptoms (prodrome), thecharacteristics of the episode itself, and the symp-toms that follow it (recovery). This must be setagainst details of previous episodes, past and fam-ily history of neurological, cardiac and psychiatricdisorders, details of medications, alcohol and illicitdrugs, social situation, occupation and driving. Cer-tain points in the history may be used to score thelikelihood of syncope or seizure.18 Patients with ahistory of prior myocardial infarction, symptoms ofcongestive cardiac failure or a family history of sud-den unexpected death before the age of 40 yearsshould be carefully assessed in view of the real pos-sibility of life-threatening ventricular tachyarrhyth-mias.

IndicationA full and detailed history with witness account isclearly the essential first approach to a patient pre-senting with blackouts.


7/12


Table 3 ECG markers predicting sudden cardiac death (after Brugada and Geelen20).

Syndrome ECG pattern

Long QT syndrome Prolonged QT intervalWolff-Parkinson-White syndrome Short PR interval, delta wave, wide QRS complexArrhythmogenic right ventricular

cardiomyopathy

Negative T waves in the right precordial leads, abnormal

deflection after the QRS complex (epsilon wave),incomplete right bundle branch block

Anterior wall myocardialinfarction with right bundlebranch block

Q waves in the precordial leads, and right bundle branch block

Dilated cardiomyopathy Low voltage in the limb and standard leads, withpreservation of the voltage in the precordial leads

Hypertrophic cardiomyopathy High QRS voltage, prominent septal Q waves in the lateralleads, and giant negative T waves in the precordial leads

Brugada syndrome ST elevation in V1V3 and right bundle branch block

Physical examination

The pulse rate and rhythm and the BP require par-ticular attention. The supine and standing BP andheart rate is sometimes suggested for all patientswith syncope. However, its main value is in pa-tients (usually elderly) with possible orthostatichypotension. In those with suspected vasovagalsyncope, the BP typically remains unchanged oreven rises a little on first standing. Blood pressuremeasured in both arms may help to diagnose brain-stem transient ischaemic attacks due to subclaviansteal syndrome. Cardiac auscultation is important

to identify structural, particularly valvular, heartdisease. Carotid sinus massage would not usuallybe undertaken in a neurology clinic without specialarrangements.

IndicationIn patients presenting with probable syncope, thephysical examination should focus on the cardio-vascular system; conventional neurological exami-nation is likely to be normal. Positive physical signsconsistent with underlying structural heart diseasesuch as a murmur or evidence of heart failure signif-icantly increase the possibility that syncope is dueto a cardiac arrhythmia.

Electrocardiogram (ECG)

Its main value in syncope is to identify a possibleunderlying cardiac cause. It identifies the definitecause of syncope in less than 5% of cases.16,19 Impor-tant abnormalities to recognise in a syncope clinicare obvious rhythm disturbances, varying degreesof conduction block (e.g. first degree heart block,bi-fascicular or trifascicular block), and patternssuggesting a predisposition to serious arrhythmias

(especially Wolff-Parkinson-White and long QT syn-

drome). It is particularly important that cliniciansinvestigating syncope recognise the ECG patternsassociated with syncope preceding sudden cardiacdeath (Table 3).16,20 Pathological Q waves signifyprior transmural myocardial infarction and implythat the patient has the substrate for scar-relatedventricular tachycardia, the commonest cause ofsudden cardiac death, frequently preceded by re-current syncope.

IndicationECG is cheap, risk free and identifies significant ab-

normalities in about 5% of people presenting withsyncope. It is therefore recommended in almost allpatients presenting with syncope, with the possibleexception of young, healthy patients with obviousvasovagal symptoms.

Echocardiography

Transthoracic echocardiography in a non-invasive,outpatient test, which should be considered earlyin the investigation of syncope. Patients with syn-cope of undetermined origin can, in general, bedivided into those with structural heart disease athigh risk of sudden cardiac death and those withentirely normal echoradiograms who are usuallyat low risk of sudden death. Evidence of priormyocardial infarction, valvular heart disease andcardiomyopathies greatly increase the possibilitythat syncope is due to life-threatening ventriculartachyarrhythmia. SUO in patients with structuralheart disease constitute between 3 and 10% of syn-cope patients. In one-third of these cases syncopeis due to ventricular tachycardia; untreated thesepatients have a 1020% annual risk of sudden deathdue to a cardiac arrest.2123 Therefore, patients


8/12


with SUO and structural heart disease should be re-ferred for urgent cardiological/electrophysiologicalassessment. The majority of patients with SUOand apparently normal hearts will have a be-nign condition such as neurally-mediated syncope.However, if the clinical features are atypical for

neurally-mediated syncope and especially if thereis family history of sudden premature death, con-sideration should be given to the possibility of aprimary arrhythmia disorder (e.g. congenital LQTS,Brugada syndrome) or conditions which may be dif-ficult to diagnose echocardiographically (e.g. hy-pertrophic cardiomyopathy, arrhythmogenic rightventricular cardiomyopathy).

IndicationEchocardiography is indicated in all patients withsyncope of undetermined origin based on a detailedhistory, physical examination and ECG analysis. In

certain circumstances, it should be obtained as amatter of urgency:

Structural heart disease, e.g. abnormal cardio-vascular examination, abnormal ECG, exercise-induced symptoms, or major cardiac risk factorsincluding age >60 years, smoker, diabetic, hyper-tensive, hyperlipidaemic patients.

Cardiac syncope, e.g. brief syncope with onsetfrom seated or lying posture, absence of pro-drome, and rapid recovery. Also cardiac syncopeshould be considered in older patients or in thosewith concomitant history of palpitations.

Echocardiography is also essential before an exer-cise test, undertaken for exertional syncope.

Exercise test

Exercise testing is used routinely in evaluating pa-tients with known or suspected coronary artery dis-ease. The role of exercise testing in investigatingsyncope is not well studied, and the direct yield ofidentifying an exercise-induced arrhythmia amongunselected syncope cases, is probably less than 1%.4

Targeted use of exercise testing aims to confirm andquantify coronary artery disease in those suspectedof having it, and in ruling out coronary disease andexercise-induced arrhythmias in patients present-ing with exertional syncope.

An echocardiogram must precede an exercise testin patients with exertional syncope, to exclude leftventricular obstruction, e.g. aortic stenosis, HCM.

IndicationAn exercise test is indicated in patients with syn-cope where

the symptoms are associated with exertion, or there is suspected coronary disease.

Prolonged ECG monitoring

The gold standard diagnostic test for cardiac syn-cope is an electrocardiographic recording duringa spontaneous syncopal attack. Non-invasive am-bulatory monitoring can be prescribed for 2448 h(Holter monitoring) or for a few weeks (continuousloop recorders). Continuous loop recorder can bepatient activated on restoration of consciousnessand also may be programmed to autocapture eventsabove or below a programmable heart rate. Certainarrhythmias such as ventricular tachycardia, if cap-tured on an ambulatory recording, would stronglysuggest the cause of a patients syncope, even ifunaccompanied by typical symptoms during the

recording. In general, however, rhythm abnormal-ities must correlate exactly with symptoms to beconsidered diagnostic. Healthy asymptomatic indi-viduals may demonstrate periods of second-degreeheart block or sinus bradycardia especially whilesleeping. Patients with significant structural heartdisease and syncope secondary to scar-relatedventricular tachycardia may demonstrate asymp-tomatic episodes of second or third degree heartblock, which is a manifestation of widespreadmyocardial destruction. These patients need care-ful assessment, as they require not only back-up

bradycardia pacing support but also implantabledefibrillator therapy. Gibson and Heitzman24 foundthat 19% of syncope patients showed diagnosticchanges on Holter monitoring: 4% had typical symp-toms with an arrhythmia (true positive: arrhyth-mogenic syncope diagnosed), and 15% had symp-toms without arrhythmia (true negative: arrhyth-mogenic syncope excluded). One study25 foundthat continuing the monitoring from 24 to 48 or72 h identified major arrhythmias in an additional11 and 15% of patients, respectively; however,these arrhythmias all occurred without typicalsymptoms.

For patients with infrequent undiagnosed syn-cope, a solid-state implantable loop recorder, e.g.Medtronic Reveal device, can record a singlelead ECG continuously up to 18 months until asymptomatic event is captured. This unit (approx-imately 5 cm 1 cm) is implanted subcutaneouslyusing local anaesthesia. It can be both patient ac-tivated and programmed to autocapture eventsabove or below a programmable heart rate. Pa-tients are reviewed every 3 months or after eachsyncopal event until a definite diagnosis is maderegarding the cardiac rhythm.


9/12


IndicationCardiac arrhythmias causing syncope are rare instructurally normal hearts. Thus, ambulatory ECGmonitoring (including longer term monitoring) isusually only indicated where

syncope occurs with suspected structural heartdisease, e.g. abnormal ECG or age over 60 years;or

in suspected arrhythmogenic syncope (brief lossof consciousness, palpitation with syncope, ab-sence of prodrome, prompt recovery);

syncope in individuals with a family history of pre-mature sudden unexpected death.

Cardiac electrophysiological (EP) study

Diagnostic EP studies involve percutaneous place-

ment of electrodes into the heart to assess the car-diac rhythm in response to atrial and ventricularstimulation protocols.

The procedure is performed under local anaes-thesia. Over 90% of patients with re-entrant tachy-cardia are inducible in the EP lab. In patients withsyncope of undetermined origin and structuralheart disease such as prior myocardial infarction EPtesting plays a useful role in risk stratification. Pa-tients with inducible ventricular tachycardia havea poor prognosis (30% mortality at 3 years) due toa high incidence of cardiac arrest and are usuallyprotected with an implantable defibrillator.26,27

Patient who are non-inducible have a better sur-vival (10% mortality at 3 years, usually due tonon-arrhythmic deaths) and are at low risk forfuture cardiac arrest. Diagnostic EP studies areperformed by placing catheters in the heart viathe femoral veins; as the arterial circulation isnot entered the risks associated with diagnostic EPstudies are substantially less than those associatedwith diagnostic cardiac catheterisation.

IndicationAn EP study is indicated in patients with recurrent

syncope and structural heart disease.

Tilt table testing

Head up passive tilt testing (HUTT) has assisted thediagnosis of vasovagal syncope since 1986.28 Thetest protocol typically involves testing the patientin the morning having fasted. After lying supine for30 min, the patient is tilted to 6080 for 20 mmHg:vasodepressor response), bradycardia (HR fall>10% baseline: cardio-inhibitory response) or both

(mixed response). Haemodynamic changes withoutsymptoms comprise a negative test. If the initialHUTT is non-diagnostic, pharmacological provoca-tions, e.g. nitrates, isoproterenol, can shorten thetest duration, though they reduce its specificity. Adrug-free HUTT is positive in approximately 50% ofpatients with suspected vasovagal syncope;30 med-ications (e.g. isoproterenol) increase the yield to64%.31 Relative contraindications to HUTT includeproximal coronary artery disease, critical mitralstenosis, clinically severe left ventricular outflowobstruction and severe cerebrovascular disease.HUTT commonly provokes attacks in patients with

psychogenic episodes.

IndicationHUTT is indicated in patients with recurrent un-explained syncope (likely to be vasovagal) wherestructural heart disease is either not suspected orhas been excluded as the cause. It is indicatedafter a single episode only if syncope occurred ina high-risk setting, e.g. while driving, or causingsignificant injury. It may also be helpful even whenvasovagal syncope is clinically definite, if demon-stration of specific haemodynamic changes might

alter management, e.g. permanent pacemakertherapy in cardio-inhibitory vasovagal syncope.32

Anecdotally, a positive HUTT helps the patient tounderstand the symptoms and can lead to improve-ment in syncope frequency.

Carotid sinus massage

Carotid sinus hypersensitivity is diagnosed byrecording the heart rate and BP responses to carotidsinus massage, ideally using continuous ECG andphasic BP monitoring. The carotid artery shouldbe auscultated first. Carotid sinus massage shouldnot be attempted in patients with suspected orknown carotid vascular disease. With the patientinitially supine and the neck slightly extended, theartery is massaged (not compressed) for up to 5 s.If the response is negative or non-diagnostic, thecontralateral artery is massaged after 15 s rest. Bi-lateral simultaneous carotid massage should neverbe attempted. The incidence of neurological com-plications of this procedure is very low at around0.14%.32

Carotid sinus syndrome is diagnosed whenmassage reproduces the patients spontaneous


10/12


symptoms together with asystole for >3 s (car-dioinhibitory), a systolic BP fall of >50 mmHg (va-sodepressive) or both (mixed).33 Haemodynamicchanges without symptoms (carotid sinus hypersen-sitivity) comprise a negative test and is induciblein about 10% of the general elderly population.

IndicationCarotid sinus massage is indicated in elderly pa-tients with recurrent unexplained syncope or falls(drop attacks), especially if the symptoms sug-gest carotid sinus syndrome.

Electroencephalogram (EEG)

Neurological investigations have a generally lowyield in patients with syncope, if there are nosymptoms or signs suggestive of seizure.34 Up to0.52% of healthy young adults have epileptiform

changes on inter-ictal EEG.

IndicationEEG is unnecessary in patients with syncope. How-ever, it may be useful where the diagnosis ofsyncope is uncertain and a spontaneous epilep-tic seizure is suspected,35 especially in a patientbelow the age of 25 years.

Simultaneous ECG and EEG monitoring

Simultaneous ECG and EEG may help to diagnose

frequent attacks, which cannot be distinguished assyncope or seizure. Video EEG recording (telemetry)might usefully include an ECG channel in the record-ing montage to identify accompanying arrhythmiasduring seizures. Ambulatory EEG and ECG withoutsimultaneous video is less useful, and has otherproblems including the limited number of availablerecording channels, and movement artefact thatsometimes simulates epileptic activity.

IndicationSimultaneously ECG and EEG monitoring may be in-dicated in patients with frequent attacks, whichcannot be distinguished on clinical grounds as ei-ther syncope or seizure.

Brain imaging

Computed tomography or magnetic resonance brainscans are usually unnecessary for patients present-ing with syncope. Intermittent obstructive hydro-cephalus caused by structural intracranial lesionsis a rare cause of syncope. Seizures with underly-ing cerebral lesions may occasionally be mistakenfor syncope. Day et al. found a diagnostic yield of

only 4% among patients presenting to an emergencyunit with transient loss of consciousness;36 all thosewith positive findings had either focal neurologicalfindings or a witnessed seizure.

Indication

Brain imaging is indicated in patients with syncopeonly if there is a significant likelihood of seizure,new onset focal neurological symptoms or signs, orif headache consistently precedes the episodes.

Carotid imaging

Carotid transient ischaemic attacks are not accom-panied by loss of consciousness. Carotid Doppler ul-trasonography is not indicated in patients with syn-cope.

Autonomic function tests

Bedside autonomic function tests are helpful to di-agnose autonomic dysfunction. The major tests arethe supine and erect BP and heart rate at 0, 1and 2 min. Other simple bedside autonomic functiontests include observing heart rate changes (or ab-sence of changes in autonomic neuropathy) on ECGmonitoring during the Valsalva manoeuvre, deepbreathing or sustained handgrip.37 Diurnal and en-vironmental factors influence the orthostatic re-sponse and so a single BP measurement unchangedby posture does not exclude intermittent ortho-

static hypotension.

IndicationBedside autonomic function tests are indicatedwhere syncope occurs immediately on standing(especially in the elderly) or if there are otherautonomic symptoms, e.g. dry mouth, urinary ur-gency/incontinence/retention, impotence, andconstipation.

Hyperventilation test

Panic disorder and hyperventilation are identifiedin around a quarter of patients with unexplainedsyncope.38 It can be helpful (to patient and clini-cian) to provoke the physical symptoms of hyper-ventilation in the clinic.

Hyperventilation testing involves either increas-ing the ventilation rate to 60 min1 or simply deepbreathing for 3 min.39 Dizziness, unsteadiness, andblurred vision commonly develop within 2030 s,especially when standing; parasthesiae in the fin-gers and face start later. About half report chestpain after three minutes of hyperventilation. Care isneeded in interpreting the result since these symp-


11/12


toms occur in anyone who hyperventilates well. Thehyperventilation syndrome is diagnosed only if thepatients typical symptoms are reproduced by themanoeuvre. For some patients with hyperventila-tion syndrome, symptoms cannot be reliably re-produced during the hyperventilation test, even on

consecutive visits.

IndicationA hyperventilation test (usually with a short screen-ing questionnaire for depression, anxiety and panicattacks) is recommended in patients with recur-rent unexplained syncope.40 The hyperventilationtest should not be performed in patients with is-chaemic heart disease, cerebrovascular disease,pulmonary insufficiency, hyperviscocity states, sig-nificant anaemia or uncontrolled hypertension.

Blood tests

Routine blood tests, e.g. full blood count, elec-trolytes, glucose, rarely give diagnostically usefulinformation in patients with syncope17 unless thereis clinical suspicion of anaemia or a metabolic dis-order. In suspected insulinoma, a 72-h fast typicallyinduces hypoglycaemic attacks with inappropriatelyhigh endogenous insulin concentrations.

IndicationMetabolic blood tests are only indicated for syn-cope in special circumstances, e.g. suspected in-

sulinoma.

Conclusion

The diagnosis of syncope is critically dependentupon careful history takingin most patients adiagnosis can be established without complicatedand expensive investigations. Nevertheless, an ECGshould be routine for all patients presenting withsyncope, and clinicians investigating such patientsmust be familiar with the common and potentiallyserious ECG abnormalities that may be associatedwith syncope. Neurologists are likely to be helpedby working closely with a cardiologist when investi-gating syncope. The selection of investigations be-yond ECG depends upon the certainty of diagnosis,the frequency and severity of attacks, and the like-lihood of an underlying cardiac cause. When cardiacdisease is likely, echocardiography, prolonged ECGmonitoring, invasive EP studies or exercise testingmay be appropriate. Where cardiac disease is notconsidered the likely cause of syncope, and theepisodes are frequent, a head up tilt table test (forvasovagal syncope) may be helpful. If syncope con-

tinues despite normal investigations, psychogeniccauses should be considered. Despite the wealthof available investigations, however, retaking thehistory is still likely to be the most valuable inves-tigation in a patient with undiagnosed blackouts.

References

1. Dermaksian G, Lamb LE. Syncope in a population of healthyyoung adults. JAMA 1958;168:12007.

2. Savage DD, Corwin L, McGee DL, et al. Epidemiologic fea-tures of isolated syncope: the Framingham Study. Stroke1985;16:6269.

3. Hauser WA, Annegers JF, Kurland LT. The incidence ofepilepsy and unprovoked seizures in Rochester, Minnesota,193584. Epilepsia 1993;34:45368.

4. Kapoor WN. Evaluation and outcome of patients with syn-cope. Medicine (Baltimore) 1990;69:16075.

5. Chadwick D, Smith D. The misdiagnosis of epilepsy. BMJ2002;

324:4956.

6. Schnipper JL, Kapoor WN. Diagnostic evaluation and man-agement of patients with syncope. Med Clin North Am2001;85:42356.

7. Smith PEM. If its not epilepsy. . . . J Neurol Neurosurg Psy-chiatry 2001;70(Suppl 2):1149.

8. Sneddon JF, Scalia G, Ward DE, et al. Exercise inducedvasodepressor syncope. Br Heart J 1994;71:5547.

9. Lempert T, Bauer M, Schmidt D. Syncope: a videometricanalysis of 56 episodes of transient cerebral hypoxia. AnnNeurol 1994;36:2337.

10. Morley CA, Perrin EJ, Grant et al. Carotid sinus syn-drome treated by pacing. Analysis of persistent symptomsand role of atrio-ventricular sequential pacing. Br Heart1982;47:41118.

11. Freeman R, Schachter SC. Autonomic epilepsy. Semin Neurol1995;15:15866.12. Blumhardt LD, Smith PEM, Owen L. Electrocardiographic

accompaniments of temporal lobe epileptic seizures. Lancet1986;1:10515.

13. Tinuper P, Bisulli F, Cerullo A, et al. Ictal bradycardia inpartial epileptic seizures: autonomic investigation in threecases and literature review. Brain 2001;124:236171.

14. Constantin I, Martins JB, Fincham RW, et al. Bradycardiaand syncope as manifestations of partial epilepsy. J Am CollCardiol 1990;15:9005.

15. Howell SJ, Blumhardt LD. Cardiac asystole associated withepileptic seizures: a case report with simultaneous EEG andECG. J Neurol Neurosurg Psychiatry 1989;52:7958.

16. Linzer M, Yang EH, Estes III NA. Diagnosing syncope: Part

1. Value of history, physical examination, and electrocar-diography. Clinical Efficacy Project of the American Collegeof Physicians. Ann Intern Med 1997;126:98996.

17. Linzer M, Yang EH, Estes III NA. Diagnosing syncope: Part 2.Unexplained syncope. Clinical Efficacy Assessment Projectof the American College of Physicians. Ann Intern Med1997;127:7686.

18. Sheldon R, Rose S, Ritchie D. Historical criteria thatdistinguish syncope from seizures. J Am Coll Cardiol2002;40:1428.

19. Hammill SC. Value and limitations of non-invasive assess-ment of syncope. Cardiol Clin 1997;15:195218.

20. Brugada A, Geelen P. Some electrocardiographic patternspredicting sudden cardiac death that every doctor shouldrecognise. Acta Cardiologica 1997;6:47384.


12/12


21. Martin GJ, Adams SL, Martin HG, et al. Prospectiveevaluation of syncope. Ann Emerg Med 1984;13:499504.

22. Kapoor W, Karpf M, Wieand S, et al. A prospective evalua-tion and follow-up of patients with syncope. N Engl J Med1983;309:197204.

23. Kapoor W. Evaluation and outcome of patients with syn-cope. Medicine 1990;69:16975.

24. Gibson TC, Heitzman MR. Diagnostic efficacy of 24-h elec-trocardiographic monitoring of syncope. Am J Cardiol1984;53:10137.

25. Bass EB, Curtiss EI, Arena VC, et al. The duration of Holtermonitoring in syncope: is 24 hours enough? Arch Intern Med1990;150:10738.

26. Gouello JP, Victor J, Tades A. Natural history of syncopeof undetermined origin with inconclusive electrophysiologicexamination. Arch Mal Coeur 1992;85:297302.

27. Twidale N, Tonkin AM. Clinical electrophysiology study inpatients with syncope of undetermined aetiology. Aust NZ

J Med 1987;17:5127.28. Parry SW, Kenny RA. Tilt table testing in the diagnosis of

unexplained syncope. Q J Med 1999;92:6239.29. Razvi SSM, Pascual J, Smith PEM. Tilt table referrals from

an epilepsy clinic. Seizure 2003;12:2959.30. Kapoor WN, Smith MA, Miller NL. Upright tilt testing in

evaluating syncope: a comprehensive literature review. AmJ Med 1994;97:7888.

31. Kapoor WN. Using a tilt table to evaluate syncope. Am JMed Sci 1999;317:1106.

32. Munro NC, McIntosh S, Lawson J, et al. Incidence of com-plications after carotid sinus massage in older patients withsyncope. J Am Geriatr Soc 1994;42:124851.

33. McIntosh SJ, Lawson J, Kenny RA. Clinical characteristicsof vasodepressor, cardioinhibitory, and mixed carotid sinussyndrome in the elderly. Am J Med 1993;95:2038.

34. Davis TL, Freemon FR. Electroencephalography should notbe routine in the evaluation of syncope in adults. ArchIntern Med 1990;150:20279.

35. SIGN (Scottish Intercolligiate Guidelines Network). 2003.http://www.sign.ac.uk/pdf/sign70.pdf (accessed 25 Jan-uary 2004).

36. Day SC, Cook EF, Funkenstein H, et al. Evaluation and out-come of emergency room visits with transient loss of con-sciousness. Am J Med 1992;73:1523.

37. Low PA. Laboratory evaluation of autonomic function. In:Low PA, editor. Clinical autonomic disorders, 2nd ed.Philadelphia: Lippincott-Raven Publishers. p. 179208.

38. Kapoor WN, Fortunato M, Hanusa BH, et al. Psychiatricillnesses in patients with syncope. Am J Med 1995;99:50512.

39. Evans RW. Neurologic aspects of hyperventilation syndrome.Semin Neurol 1995;15:11525.

40. Linzer M, Felder A, Hackel A, et al. Psychiatric syncope: anew look at an old disease. Psychosomatics 1990;31:1818.
http://www.sign.ac.uk/pdf/sign70.pdf

syncope intvestigations

Documents