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Syncope in patients with structural heart diseaseDavid O. Arnar

From the Division of Cardiology, Department of Internal Medicine, Landsptali The National University Hospital of Iceland, Reykjavik,Iceland

Abstract. Arnar DO (Landsptali The NationalUniversity Hospital of Iceland, Reykjavik,Iceland). Syncope in patients with structuralheart disease (Review). J Intern Med 2013; 273:336344.

Syncope is a common condition. It is frequentlydue to a benign cause, but may occasionally be dueto a potentially life-threatening disorder. The pres-ence of structural heart disease in patients with

syncope is associated with a poor prognosis andmay be a predictor of sudden cardiac death. Inpatients who present with syncope, the presence ofstructural heart disease and primary electrophys-iological disorders should be considered and fur-ther cardiac evaluation performed as indicated bythe clinical history, physical examination andelectrocardiographic findings.

Keywords: arrhythmia, heart disease, syncope.

Introduction

Syncope is defined as a sudden, but transient lossof consciousness accompanied by a loss of posturaltone. Recovery is spontaneous and does notrequire the use of cardiopulmonary resuscitation.Syncope is a common condition and the differentialdiagnosis is extensive. It has been reported that thefrequency of syncope amongst users of emergencydepartments in Europe is approximately 1% [1, 2].The causes of syncope are frequently benign, butcan occasionally be due to a potentially life-threat-ening disorder [3]. Because of the transient natureof syncope and some of its causes, determination ofthe underlying mechanism can be challenging. Acomprehensive initial clinical history along with adetailed physical examination and an electrocar-diogram (ECG) are essential for determining thepossible causes as well as the need for furtherdiagnostic testing. However, despite a thoroughevaluation, the cause of syncope may remainunknown in approximately a third of patients.

The causes of syncope are heterogeneous and varywith age (Table 1). Neurocardiogenic (vasovagal)syncope is most common in patients under the ageof 40 years and usually has a favourable prognosis[4]. More serious, but less frequent causes ofsyncope in those under the age of 40 includehypertrophic cardiomyopathy and the so-calledprimary electrophysiological disorders, which canresult in ventricular tachycardia (VT) and fibrilla-tion [5]. In individuals over the age of 40 years,cardiac mechanical causes, such as heart failureand aortic stenosis, in addition to arrhythmias are

more common [6]. Furthermore, conditions suchas orthostatic hypotension and drug-related syn-cope are not uncommon in older age groups. In theelderly, syncope is also more commonly due to acombination of factors. The presence of structuralheart disease increases the likelihood of a seriouscause of syncope, such as malignant ventriculararrhythmias.

There are two main goals in the evaluation ofpatients with syncope. The first aim is to establishthe cause of the syncopal event. Secondly, patientsare stratified according to risk, including identifi-cation of those at high risk of sudden cardiac deathor of recurrent syncope or physical injury [5, 6].

High-risk features of syncope

Cardiac syncope can predict sudden cardiac death[7]. Individuals who present with syncope and areat high risk of subsequent sudden cardiac death,frequently have a history of structural heart dis-ease along with clinical or ECG characteristicssuggestive of a serious arrhythmia [6]. Thesecharacteristics include heart failure with a severelyreduced ejection fraction or the presence of myo-cardial scar tissue from previous myocardialinfarction. Clinical features suggestive of a seriouscause of syncope include occurrence during eitherexertion or whilst supine. Prodromal symptoms ofchest pain, acute shortness of breath and palpita-tions with sudden onset of dizziness may allsuggest a possible serious cardiac cause. A higherrisk of sudden cardiac death is also indicated by anECG showing one or more of the following

336 2013 The Association for the Publication of the Journal of Internal Medicine

Review

abnormalities: nonsustained VT, bifascicular blockor intraventricular conduction delay (QRS > 120ms), a pre-excited QRS, abnormally prolonged orshort QT interval, a Brugada syndrome pattern ornegative T waves in the precordial leads along withan epsilon wave consistent with arrhythmogenicright ventricular cardiomyopathy [6, 8]. Patientspresenting with syncope and one or more of theabove ECG abnormalities are candidates for hos-pital admission. These individuals should receivecontinuous ECG monitoring and further diagnosticevaluation whilst in hospital; consultation with anarrhythmia specialist should also be considered.

A diagnosis of a cardiac cause of syncope hasimportant prognostic implications. Studies com-paring mortality after syncope according to likelymechanism have consistently shown that patientswith a cardiac cause have a higher mortality thanthose with a noncardiac cause [9]. In the largestsuch study of over 400 patients with a follow-up ofmore than 60 months, the mortality rate duringfollow-up was 50% in patients with a cardiac causecompared with rates of 31% and 24%, respectively,in those with a noncardiac or unknown cause [10].

A variety of structural heart diseases can result insyncope (Table 2) [6]. Disorders commonly associ-ated with syncope include ischaemic heart disease

(especially if associated with depressed left ven-tricular function), nonischaemic dilated cardiomy-opathy and severe aortic stenosis. Other lessfrequent, but nevertheless important causes arehypertrophic cardiomyopathy and arrhythmogenicright ventricular cardiomyopathy (previouslytermed dysplasia). Although not classified as struc-tural heart diseases, but rather as genetic disor-ders that underlie primary electrophysiologicaldisease, the long QT interval syndrome (LQTS),short QT syndrome, catecholaminergic polymor-phic VT and Brugada syndrome are also worthconsidering as relatively infrequent, but seriouscauses of syncope. Similarly, an accessory atrio-ventricular pathway causing delta wave on theECG may represent uncommon causes of severesyncope. In the latter case, atrial fibrillation can beassociated with extremely high ventricular ratesdue to rapid conduction over the accessory path-way, which may sometimes lead to syncope andeven cardiac arrest.

Myocarditis, pulmonary embolism, cardiac tamp-onade, atrial myxoma, severe pulmonary hyper-tension and certain congenital heart diseases(including those previously repaired) are structuralheart disorders that are occasionally associatedwith syncope [6].

A family history of sudden cardiac death, especiallyat a young age, should alert to the possibility of aninherited arrhythmogenic disease [5]. Likewise,

Table 1 Causes of syncope according to age

Patients < 40 years of age Patients 40 years of ageNeurocardiogenica Cardiacc

Psychiatrica Mechanical

Long QT syndromeb Arrhythmic

(tachy- or

bradyarrhythmias)

Brugada syndromeb Orthostatic hypotensiona

WolfParkinsonWhite

syndromebDrug relateda

Arrhythmogenic right

ventricular

cardiomyopathyb

Multifactoriala

Ventricular

cardiomyopathyb

Hypertrophic

cardiomyopathyb

aUsually benign.bInfrequent, but not benign.cGenerally not benign.

Table 2 Structural heart diseases that can lead to syncope

Commonly cause syncope Rarely cause syncope

Ischaemic heart disease Myocarditis

Nonischaemic dilated

cardiomyopathy

Pulmonary embolism

Aortic stenosis Cardiac tamponade

Hypertrophic cardiomyopathy Atrial myxoma

Arrhythmogenic right

ventricular cardiomyopathy

Severe pulmonary

hypertension

(Primary electrophysiological

disorders: long QT

syndrome, short QT

syndrome, Brugada

syndrome,

catecholaminergic

polymorphic ventricular

tachycardia)

Aortic dissection

Congenital heart

disease

D. O. Arnar Review: Syncope in heart disease

2013 The Association for the Publication of the Journal of Internal Medicine 337Journal of Internal Medicine, 2013, 273; 336344

any history of cardiovascular problems in theindividual presenting with syncope may be impor-tant when attempting to narrow the differentialdiagnosis.

However, it is noteworthy that the presence ofstructural heart disease per se does not neces-sarily imply that the syncopal event is caused bythe underlying heart disorder. Patients with anunderlying heart condition can also have rela-tively benign causes of syncope, such as neuro-cardiogenic or drug-induced syncope. Drug-induced syncope can be overlooked, especiallyin elderly patients who may be taking a numberof different cardiac medications [11]. Frequentlyused drugs amongst patients with heart diseaseinclude beta blockers, diuretics and vasodilators.All these drugs could alone or in combinationpredispose patients to episodes of haemodynamiccompromise due to bradycardia and/or hypoten-sion in different clinical situations. Furthermore,the use of antiarrhythmic medications can beassociated with proarrhythmia and syncope, oreven cardiac arrest. A complete medication his-tory including recently started prescription andover the counter drugs should therefore alwaysbe obtained.

Mechanisms of syncope in structural heart disease

The most frequent cause of syncope in patientswith structural heart disease are arrhythmiascausing decreased cardiac output, haemodynamicimpairment and a subsequent decrease in cerebralblood flow [3]. Both bradyarrhythmias and tachy-cardias can lead to syncope. There are a number offactors that determine whether or not a tachyar-rhythmia leads to syncope, including the type ofarrhythmia [12]. In this regard, supraventriculartachyarrhythmias are generally better toleratedthan VTs and the faster the heart rate during thearrhythmia, the less well it is tolerated. Patientswith impaired left ventricular ejection fraction areusually less able to tolerate fast heart rhythms. Theposture of a patient during the onset of thearrhythmia also has an influence on tolerability.Finally, the use of vasoactive drugs may adverselyaffect the haemodynamic response during tachy-cardia.

Bradycardia due to sick sinus syndrome oradvanced atrioventricular block is another com-mon cause of syncope in patients with heartdisease. Interruption of cerebral blood flow for

810 s usually produces loss of consciousness,although briefer pauses can cause near syncope[7]. In individuals with a pacemaker, a devicemalfunction needs to be ruled out.

Other possible causes of cardiogenic syncopeinclude low output states, for example with eitherischaemic or dilated cardiomyopathy, which cansometimes be further exacerbated if the patient istaking vasoactive medications, as is common inthose who have these disorders. Conditions suchas aortic stenosis and severe hypertrophic cardio-myopathy may cause mechanical outflow obstruc-tion from the left ventricle, especially duringexertion [13]. However, aortic stenosis can alsocause syncope via inappropriate reflex vasodilata-tion [6].

Initial evaluation of patients with suspected cardiac syncope

As mentioned above, there are a number of findingsof the medical history, physical examination orECG that should alert to the possibility of a cardiaccause of syncope. A number of studies have beenconducted to determine which factors in the clin-ical history may predict a serious cause of syncope.Calkins et al. found that male gender, age over45 years and no more than two episodes of syncopepredicted either VT or atrioventricular block as thecause of syncope [14]. In addition, syncope whilstsupine, duration of symptoms less than 4 yearsand blurred vision were reported to be independentpredictors of cardiac syncope [15]. Furthermore,Sheldon et al. demonstrated that male gender andage at onset of syncope over 35 years predicted VTas the syncopal cause rather than a neurocardio-genic aetiology [16].

Clinical risk scores have been developed to predictthe outcome in patients presenting with syncope[1, 1719]. Many of these risk scores have keycommon factors that increase the risk of a pooroutcome, including abnormal ECG, age above40 years and history of heart failure or myocardialinfarction, which highlights the importance ofstructural heart disease in the prognosis of syn-cope.

The initial evaluation is therefore critical inpatients with syncope. A clinical history, physicalexamination and ECG should always be conductedif there is suspicion of cardiac syncope. Furtherdiagnostic work-up is guided by the findings of theinitial evaluation.


338 2013 The Association for the Publication of the Journal of Internal MedicineJournal of Internal Medicine, 2013, 273; 336344

History

The evaluation of syncope begins with a thoroughclinical history. This includes a detailed assess-ment of the syncopal event including prodromalsymptoms and the immediate aftermath. In partic-ular patients should be asked how they felt uponawakening after loss of consciousness as this canbe helpful in differentiating between syncope andother causes of loss of consciousness, such asseizures. The absence of prodromal symptoms canbe consistent with syncope due to arrhythmia,especially bradyarrhythmia. Chest pain, shortnessof breath and tachypalpitations are also indicativeof cardiac syncope. The observations of witnessesto the event are often helpful.

Physical examination

Soon after the event, a detailed physical examina-tion should be carried out, including measurementof blood pressure (both supine and standing). Inparticular, the cardiovascular examination shouldinclude evaluation of jugular venous distension,murmurs or additional heart sounds on cardiacauscultation and displaced point of maximalimpulse. Carotid artery auscultation should alsobe performed for evaluation of bruit and the qualityof the carotid pulse. Lung auscultation shoulddetermine the presence of rales and the respiratoryrate and pattern. The quality of peripheral pulsesneeds to be evaluated. A neurological examinationshould be performed to assess any abnormalities ofcognition, speech, motor strength, sensation orvisual fields.

ECG

The 12-lead ECG is an important tool in the initialevaluation of syncope. The ECG can provide infor-mation about heart rate and rhythm, and thepresence of ongoing ischaemia (T wave changes orST depression) or a new infarction (ST elevation). Inaddition, the presence of Q waves should be notedas an indication of a prior myocardial infarction ora myocardial scar. Changes suggestive of leftventricular hypertrophy might be present on theECG. The QT interval should be measured andevaluated for abnormally long or short QT inter-vals. The presence of a delta wave, Brugadapattern, bundle branch block or atrioventricularconduction abnormalities should also be noted. Itis important to acknowledge that some of the ECGchanges associated with these disorders may only

be present intermittently and therefore one ECGmay not be enough to rule them out. Arrhythmo-genic right ventricular cardiomyopathy is a rela-tively rare disorder with ECG characteristics of Twave inversion in the anteroseptal leads and epsi-lon waves.

Blood tests

Whilst blood tests are generally not considered avaluable part of the diagnosis of syncope, a com-plete blood count and electrolyte levels should bemeasured in most instances. In selected patients, ifthere is suspicion of acute ischaemia or infarction,cardiac biomarkers, preferably a troponin, shouldbe evaluated. In some cases, more than one tropo-nin test may be needed to rule out myocardialinfarction. If a pulmonary embolus is suspected,measurement of D-dimer levels may be helpful.

Echocardiogram

The echocardiogram is a relatively simple noninva-sive test that can easily be performed at the bedside,even in the emergency department. This test canprovide useful information, especially if structuralheart disease is suspected or if a patient with knownheart disease presents with syncope. The echocar-diogram provides a good estimate of left ventricularfunction, including signs of regional wall motionabnormalities that are consistent with coronaryartery disease. In addition, left ventricular size andthickness are readily visualized by this technique.The presence of valvular heart disease, includingaortic stenosis, can be evaluated. Tricuspid regur-gitation, particularly if accompanied by dilatation ofthe right ventricle, raises suspicion of a pulmonaryembolus. Right ventricular dilatation and thinningof the wall may be present in conditions such asarrhythmogenic right ventricular cardiomyopathy.

ECG monitoring

Individuals with syncope who have evidence ofstructural heart disease are candidates for hospitaladmission for continuous telemetry. Holter moni-toring, for 24 h or longer, is frequently used forfurther evaluation of heart rate and rhythm inpatients with syncope. The implantable loop recor-der, a small wireless monitor placed subcutane-ously in the chest, is becoming increasingly usedfor long-term ECG monitoring. Storage of ECGtracings can be activated either by prespecifiedcriteria or by the patients during symptoms. This is



a promising tool for use in those with recurrentsyncope of unknown cause [20]. The battery of themost recent loop recorders can last for up to36 months. It is very important when interpretingthe results of rhythm monitoring to correlatesymptoms with the results of the ECG tracings.

Syncope in patients with suspected or known coronary arterydisease

The presence of ischaemic heart disease increasesthe risk of syncope being due to ventriculararrhythmias. This, in particular, applies to indi-viduals with a left ventricular ejection fraction ofless than 35%40%. The risk of death in patientswith syncope and coronary artery disease isdirectly proportional to the severity of left ventric-ular dysfunction [5].

The evaluation of patients with syncope who are atrisk of coronary artery disease should include anevaluation for myocardial ischaemia as well as forthe signs of previous myocardial infarction. Thechoice of initial tests may vary according to thepresentation and the level of suspicion of ischae-mia, but might include exercise stress testing or amyocardial perfusion imaging study. It is notewor-thy that syncope can be the only presenting symp-tom of myocardial infarction in elderly patients.

In patients with coronary artery disease and aseverely depressed ejection fraction (35%40%), a cardiac elec-trophysiology study may be indicated for furtherrisk stratification. The prognosis of patients with anormal electrophysiological result, under thesecircumstances, is favourable [24].

An electrophysiology study is performed by plac-ing catheters in the right-sided chambers of the

heart via venous puncture, usually in the groin.Programmed stimulation of the ventricles is usedto evaluate the risk of developing VT [25].Although the induction of monomorphic VT isconsidered a definite abnormality, the induction ofventricular fibrillation is nonspecific. Sinus nodefunction and atrioventricular conduction are alsotested, but the sensitivity for these abnormalitiesis poor [26]. Inducibility of VT is associated with ahigh risk of sudden cardiac death whereas non-inducibility predicts a low risk of sudden cardiacdeath [27]. The value of the electrophysiologystudy in patients with normal left ventricularfunction and no coronary artery disease is rela-tively low [28].

It is worth noting that ICD-treated patients remainat risk of syncope because only the risk of suddencardiac death is being assessed. This implies theneed for identification of the precise mechanism ofsyncope in these patients and specific treatment ifpossible [6].

In patients with coronary artery disease, if thesuspicion of a brady- or tachyarrhythmia is highdespite a normal electrophysiological evaluation,an implantable loop recorder may be considered.

Syncope and nonischaemic dilated cardiomyopathy

Nonischaemic dilated cardiomyopathy, where leftventricular function is reduced due to reasonsother than as a consequence of coronary arterydisease, can also be associated with syncope.Likely causes are ventricular arrhythmias, brad-yarrhythmias and orthostatic hypotension, eitherdue to a decreased cardiac output or as a side effectof the medications used to treat the dilated cardio-myopathy. Syncope is an ominous sign in thispopulation; in one series, almost half of thepatients presenting with this symptom had diedsuddenly within 1 year of presentation [29]. It isinteresting that in this same study, 70% of thosewho presented with VT or sudden cardiac deathhad a prior syncopal event.

As with ischaemic cardiomyopathy, an ICD isindicated for those who have an ejection fractionof less than 35% [21]. However, the data on themortality benefit of a defibrillator are not as robustfor nonischaemic as for ischaemic cardiomyopa-thy. The DEFINITE trial enrolled only patients withnonischaemic heart failure and, although therewas a significant reduction in sudden death, there



was only a borderline significant reduction inoverall mortality [30].

Invasive electrophysiology assessment is not ashelpful a risk stratification tool for those withnonischaemic cardiomyopathy as for those withcoronary artery disease. In a small study ofpatients with nonischaemic cardiomyopathy,unexplained syncope, a normal electrophysiologystudy, and who were subsequently treated with anICD, 50% received appropriate therapy with adefibrillator in the first 2 years after implantation[31]. Thus, the implications of a normal electro-physiology study in patients with nonischaemiccardiomyopathy are not as clear as for those withcoronary artery disease and preserved ejectionfraction.

As for patients with ischaemic cardiomyopathy, animplantable loop recorder may be considered inthose with nonischaemic cardiomyopathy in whomleft ventricular function is relatively preserved(>35%40%), when detailed evaluation has notdemonstrated abnormalities, but arrhythmias arestill strongly suspected.

Syncope in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is a relatively com-mon (1 : 500) inherited disease that is caused bymutations in genes encoding sarcomere proteins[32, 33]. There are different forms of hypertrophy ofthe left ventricle, but asymmetric septal hypertro-phy is the most common. This type involvesprimarily the proximal and mid portion of theinterventricular septum. The disease is suspectedif the ECG shows signs of hypertrophy withinverted T waves in the precordial leads, particu-larly when the degree of myocardial thickness issevere. The condition is then confirmed by animaging study, usually either echocardiography orcardiac magnetic resonance imaging (MRI).

In hypertrophic cardiomyopathy, the normal cellu-lar architecture is disrupted in the hypertrophiedarea, and extensive fibrosis (frequently seen as lategadolinium enhancement on MRI) can increase therisk of malignant ventricular arrhythmias [34].This can lead to syncope or even sudden cardiacdeath. The occurrence of syncope (particularlywithin the previous 6 months) in hypertrophiccardiomyopathy is serious and increases the riskof sudden cardiac death five-fold [35]. Other riskfactors for serious arrhythmias include prior his-

tory of resuscitated cardiac arrest, family historyof sudden death, nonsustained VT, marked(30 mm) hypertrophy and decreased blood pres-sure with exercise [35]. Invasive electrophysiologyassessment is not particularly helpful for riskstratification of this condition.

Despite the high risk of ventricular arrhythmias inhypertrophic cardiomyopathy, syncope in this dis-order can be caused by a variety of mechanisms.Individuals with hypertrophic cardiomyopathy areat increased risk of atrial fibrillation which canimpact the clinical course of the disease [36].Impaired left ventricular relaxation and heart fail-ure can result in left atrial enlargement and atrialfibrillation. The latter is associated with increasedmorbidity and mortality due to loss of activediastolic left ventricular filling and decreased dia-stolic filling time with rapid ventricular rates.Patients with severe obstruction of the left ventric-ular outflow tract may experience syncope duringexercise.

The main treatment for patients at high risk ofsudden death is an ICD. This device is recom-mended for patients resuscitated from suddencardiac death or sustained ventricular tachycar-dia and is considered a reasonable option if thereis a family history of sudden cardiac death,maximum wall thickness of 30 mm or recentunexplained syncope [35]. In those with nonsu-stained VT or an abnormal blood pressureresponse to exercise, an ICD might be useful incertain circumstances. Beta blockers are fre-quently prescribed and drugs such as amioda-rone and disopyramide may also be useful incertain situations.

Arrhythmogenic right ventricular cardiomyopathy and syncope

Arrhythmogenic right ventricular cardiomyopathyis a relatively rare disease that is associated withfamily clustering and characterized by fibrous andfatty replacement of the right ventricular myocar-dium [37]. The fatty/fibrous tissue may be asubstrate for ventricular arrhythmias causing syn-cope or even sudden cardiac death. Arrhythmo-genic right ventricular cardiomyopathy usuallyaffects only the right ventricle although occasion-ally the left ventricle can also be involved. Thiscondition may be the cause of up to one-fifth ofsudden deaths in individuals under the age of35 years [5]. Syncope or sudden death may be thefirst manifestation of the disease.



Arrhythmogenic right ventricular cardiomyopathycan be difficult to diagnose and the signs are oftensubtle. The ECG may show epsilon waves andinverted T waves in leads V1V3. An echocardio-gram may show a dilated and thin-walled rightventricle. A cardiac MRI usually shows right ven-tricular dilatation and fatty/fibrous replacement ofthe ventricle in addition to localized microaneu-rysm formation. The role of an electrophysiologyinvestigation in arrhythmogenic right ventriculardysplasia remains unclear. It has been shown thatdefibrillator therapy can be useful for treatment ofmalignant arrhythmias in this condition.

Syncope in aortic stenosis

Aortic stenosis is a disorder of calcific degenerationof the aortic valve and, with the ageing of Westernpopulations, has become themost commonvalvularheart disease inEurope. Syncope is usually a sign ofadvanced aortic stenosis. The cause of syncope inpatients with advanced aortic stenosis is likely to bemultifactorial. In general, syncope with aortic ste-nosis occurs with exercise. It has been presumedthat the reduced degree of valve opening inhibits thenecessary increase in cardiac output whilst periph-eral vascular resistance falls on exertion. Otherproposed mechanisms include a vasodepressorresponse which is triggered by increased left ven-tricular pressure during exercise in patients withaortic stenosis [13, 38]. Although severe aorticstenosis is relatively rare amongst individuals whopresent with syncope, it is an important potentialdiagnosis and usually suspected after clinicalexamination including cardiac auscultation. Thediagnosis is confirmed by echocardiography. Thetreatment is, in most cases, valve replacement.

Primary electrophysiological disorders

Although primary electrophysiological disordersare not in fact structural heart diseases, they areimportant causes of cardiac syncope, particularlyin young individuals. These disorders include theinherited channelopathies, LQTS, short QT syn-drome and Brugada syndrome. Whilst they can allbe diagnosed with an ECG, the findings may besubtle and dynamic. Pharmacological provocationcan be helpful if there is suspicion of or Brugadasyndrome, but the ECG does not show typical type1 changes.

Catecholaminergic polymorphic ventricular tachy-cardia is most frequent due to an inherited defect

in the ryanodine receptor in cardiac myocytes. Thisdefect increases the risk of polymorphic VT duringexertion or with elevated heart rates [39]. There areno distinct abnormalities on the resting ECG, butpolymorphic VT can be seen during an exercisestress test. An ICD is commonly used to treat high-risk patients with a primary electrophysiologicaldisorder.

The future: a role for genetics?

Genetic testing for various disorders that cancause syncope, including the most commonmutations causing LQTS, has become readilyavailable. In addition, tests for mutations associ-ated with Brugada syndrome and catechola-minergic polymorphic VT have becomecommercially available. Testing for sarcomericmutations involved in hypertrophic cardiomyopa-thy and desmosomal protein mutations in ar-rhythmogenic right ventricular cardiomyopathy isalso possible.

At present, the optimal use of genetic testing inpatients who have survived a cardiac arrest or hada suspected cardiac syncopal event is still unde-cided. However, genetic testing has been usedpostmortem (molecular autopsy) in cases in whichthe apparent cause of sudden death is unknown,but a primary arrhythmia suspected based on theclinical circumstances and lack of evidence ofstructural heart disease. Recently, in a large seriesof unexplained cardiac sudden deaths, genetictesting achieved a diagnosis in 34% of cases thatwould otherwise have remained unexplained [40].The Heart Rhythm Society and the EuropeanHeart Rhythm Association have recently issuedan expert consensus statement on the use ofgenetic testing for channelopathies and cardiomy-opathies [41]. In this comprehensive document,the indications for genetic testing for these disor-ders are reviewed.

There have been further advances in the under-standing of the potential genetic contribution tocommon causes of syncope such as sick sinussyndrome as well as variants that modulate impor-tant electrophysiological parameters such as heartrate, PR interval and QRS duration [42, 43].Whether or how this will influence futureapproaches to common problems such as syncoperemains unclear (Fig. 1), but it is likely that geneticinformation will play an increasing role in medicaldecision making in the coming decades.



Summary

In patients who present with syncope, the presenceof structural heart disease should be consideredand further cardiac evaluation performed as indi-cated by the clinical history, physical examinationand ECG findings. The presence of structural heartdisease in patients with syncope is associated witha poor prognosis and may be a predictor of suddencardiac death. A family history of sudden cardiacdeath, especially at a young age, should always benoted in individuals with syncope, as this may bean indicator of an inherited disorder that couldlead to life threatening arrhythmias.

Conflict of interest statement

No conflict of interest was declared.

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Correspondence: David O. Arnar MD PhD, EMPH, Division of

Cardiology, Office 14F, Department of Internal Medicine, Land-

sptali The National University Hospital of Iceland, Hringbraut,

101 Reykjavik, Iceland.

(fax: +354 543 6467; e-mail: [email protected]).



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