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Click here for more articles from the SYNCOPE symposium doi: 10.1111/joim.12027 Syncope in patients with structural disease

David O. Arnar

From the Division of , Department of Internal Medicine, Landspıtali – The National University Hospital of Iceland, Reykjavik, Iceland

Abstract. Arnar DO (Landspıtali – The National syncope is associated with a poor prognosis and University Hospital of Iceland, Reykjavik, may be a predictor of sudden cardiac death. In Iceland). Syncope in patients with structural patients who present with syncope, the presence of heart disease (Review). J Intern Med 2013; 273: and primary electrophys- 336–344. iological disorders should be considered and fur- ther cardiac evaluation performed as indicated by Syncope is a common condition. It is frequently the clinical history, and due to a benign cause, but may occasionally be due electrocardiographic findings. to a potentially life-threatening disorder. The pres- ence of structural heart disease in patients with Keywords: , heart disease, syncope.

more common [6]. Furthermore, conditions such Introduction as orthostatic and drug-related syn- Syncope is defined as a sudden, but transient loss cope are not uncommon in older age groups. In the of accompanied by a loss of postural elderly, syncope is also more commonly due to a tone. Recovery is spontaneous and does not combination of factors. The presence of structural require the use of cardiopulmonary resuscitation. heart disease increases the likelihood of a serious Syncope is a common condition and the differential cause of syncope, such as malignant ventricular diagnosis is extensive. It has been reported that the . frequency of syncope amongst users of emergency departments in Europe is approximately 1% [1, 2]. There are two main goals in the evaluation of The causes of syncope are frequently benign, but patients with syncope. The first aim is to establish can occasionally be due to a potentially life-threat- the cause of the syncopal event. Secondly, patients ening disorder [3]. Because of the transient nature are stratified according to risk, including identifi- of syncope and some of its causes, determination of cation of those at high risk of sudden cardiac death the underlying mechanism can be challenging. A or of recurrent syncope or physical injury [5, 6]. comprehensive initial clinical history along with a detailed physical examination and an electrocar- High-risk features of syncope diogram (ECG) are essential for determining the possible causes as well as the need for further Cardiac syncope can predict sudden cardiac death diagnostic testing. However, despite a thorough [7]. Individuals who present with syncope and are evaluation, the cause of syncope may remain at high risk of subsequent sudden cardiac death, unknown in approximately a third of patients. frequently have a history of structural heart dis- ease along with clinical or ECG characteristics The causes of syncope are heterogeneous and vary suggestive of a serious arrhythmia [6]. These with age (Table 1). Neurocardiogenic (vasovagal) characteristics include with a severely syncope is most common in patients under the age reduced ejection fraction or the presence of myo- of 40 years and usually has a favourable prognosis cardial scar tissue from previous myocardial [4]. More serious, but less frequent causes of infarction. Clinical features suggestive of a serious syncope in those under the age of 40 include cause of syncope include occurrence during either hypertrophic and the so-called exertion or whilst supine. Prodromal symptoms of primary electrophysiological disorders, which can , acute shortness of breath and palpita- result in ventricular (VT) and fibrilla- tions with sudden onset of may all tion [5]. In individuals over the age of 40 years, suggest a possible serious cardiac cause. A higher cardiac mechanical causes, such as heart failure risk of sudden cardiac death is also indicated by an and aortic , in addition to arrhythmias are ECG showing one or more of the following

336 ª 2013 The Association for the Publication of the Journal of Internal Medicine D. O. Arnar Review: Syncope in heart disease

Table 1 Causes of syncope according to age Table 2 Structural heart diseases that can lead to syncope

Patients < 40 years of age Patients  40 years of age Commonly cause syncope Rarely cause syncope Neurocardiogenica Cardiacc Ischaemic heart disease Myocarditis Psychiatrica Mechanical Nonischaemic dilated Pulmonary Long QT syndromeb Arrhythmic cardiomyopathy (tachy- or bradyarrhythmias) Hypertrophic cardiomyopathy Atrial Brugada syndromeb Orthostatic hypotensiona Arrhythmogenic right Severe pulmonary Wolf–Parkinson–White Drug relateda ventricular cardiomyopathy syndromeb (Primary electrophysiological Aortic Arrhythmogenic right Multifactoriala disorders: long QT Congenital heart ventricular syndrome, short QT disease cardiomyopathyb syndrome, Brugada Ventricular syndrome, cardiomyopathyb catecholaminergic Hypertrophic polymorphic ventricular cardiomyopathyb tachycardia) aUsually benign. bInfrequent, but not benign. (especially if associated with depressed left ven- cGenerally not benign. tricular function), nonischaemic dilated cardiomy- opathy and severe aortic stenosis. Other less abnormalities: nonsustained VT, frequent, but nevertheless important causes are or intraventricular conduction delay (QRS > 120 hypertrophic cardiomyopathy and arrhythmogenic ms), a pre-excited QRS, abnormally prolonged or right ventricular cardiomyopathy (previously short QT interval, a pattern or termed dysplasia). Although not classified as struc- negative T waves in the precordial leads along with tural heart diseases, but rather as genetic disor- an epsilon wave consistent with arrhythmogenic ders that underlie primary electrophysiological right ventricular cardiomyopathy [6, 8]. Patients disease, the long QT interval syndrome (LQTS), presenting with syncope and one or more of the short QT syndrome, catecholaminergic polymor- above ECG abnormalities are candidates for hos- phic VT and Brugada syndrome are also worth pital admission. These individuals should receive considering as relatively infrequent, but serious continuous ECG monitoring and further diagnostic causes of syncope. Similarly, an accessory atrio- evaluation whilst in hospital; consultation with an ventricular pathway causing delta wave on the arrhythmia specialist should also be considered. ECG may represent uncommon causes of severe syncope. In the latter case, atrial fibrillation can be A diagnosis of a cardiac cause of syncope has associated with extremely high ventricular rates important prognostic implications. Studies com- due to rapid conduction over the accessory path- paring mortality after syncope according to likely way, which may sometimes lead to syncope and mechanism have consistently shown that patients even . with a cardiac cause have a higher mortality than those with a noncardiac cause [9]. In the largest Myocarditis, , cardiac tamp- such study of over 400 patients with a follow-up of onade, atrial myxoma, severe pulmonary hyper- more than 60 months, the mortality rate during tension and certain congenital heart diseases follow-up was 50% in patients with a cardiac cause (including those previously repaired) are structural compared with rates of 31% and 24%, respectively, heart disorders that are occasionally associated in those with a noncardiac or unknown cause [10]. with syncope [6].

A variety of structural heart diseases can result in A family history of sudden cardiac death, especially syncope (Table 2) [6]. Disorders commonly associ- at a young age, should alert to the possibility of an ated with syncope include ischaemic heart disease inherited arrhythmogenic disease [5]. Likewise,

ª 2013 The Association for the Publication of the Journal of Internal Medicine 337 Journal of Internal Medicine, 2013, 273; 336–344 D. O. Arnar Review: Syncope in heart disease

any history of cardiovascular problems in the 8–10 s usually produces loss of consciousness, individual presenting with syncope may be impor- although briefer pauses can cause near syncope tant when attempting to narrow the differential [7]. In individuals with a pacemaker, a device diagnosis. malfunction needs to be ruled out.

However, it is noteworthy that the presence of Other possible causes of cardiogenic syncope structural heart disease per se does not neces- include low output states, for example with either sarily imply that the syncopal event is caused by ischaemic or , which can the underlying heart disorder. Patients with an sometimes be further exacerbated if the patient is underlying heart condition can also have rela- taking vasoactive medications, as is common in tively benign causes of syncope, such as neuro- those who have these disorders. Conditions such cardiogenic or drug-induced syncope. Drug- as aortic stenosis and severe hypertrophic cardio- induced syncope can be overlooked, especially myopathy may cause mechanical outflow obstruc- in elderly patients who may be taking a number tion from the left ventricle, especially during of different cardiac medications [11]. Frequently exertion [13]. However, aortic stenosis can also used drugs amongst patients with heart disease cause syncope via inappropriate reflex vasodilata- include beta blockers, diuretics and vasodilators. tion [6]. All these drugs could alone or in combination predispose patients to episodes of haemodynamic Initial evaluation of patients with suspected cardiac syncope compromise due to and/or hypoten- sion in different clinical situations. Furthermore, As mentioned above, there are a number of findings the use of antiarrhythmic medications can be of the medical history, physical examination or associated with proarrhythmia and syncope, or ECG that should alert to the possibility of a cardiac even cardiac arrest. A complete medication his- cause of syncope. A number of studies have been tory including recently started prescription and conducted to determine which factors in the clin- over the counter drugs should therefore always ical history may predict a serious cause of syncope. be obtained. Calkins et al. found that male gender, age over 45 years and no more than two episodes of syncope predicted either VT or as the Mechanisms of syncope in structural heart disease cause of syncope [14]. In addition, syncope whilst The most frequent cause of syncope in patients supine, duration of symptoms less than 4 years with structural heart disease are arrhythmias and blurred vision were reported to be independent causing decreased cardiac output, haemodynamic predictors of cardiac syncope [15]. Furthermore, impairment and a subsequent decrease in cerebral Sheldon et al. demonstrated that male gender and flow [3]. Both bradyarrhythmias and tachy- age at onset of syncope over 35 years predicted VT cardias can lead to syncope. There are a number of as the syncopal cause rather than a neurocardio- factors that determine whether or not a tachyar- genic aetiology [16]. rhythmia leads to syncope, including the type of arrhythmia [12]. In this regard, supraventricular Clinical risk scores have been developed to predict tachyarrhythmias are generally better tolerated the outcome in patients presenting with syncope than VTs and the faster the heart rate during the [1, 17–19]. Many of these risk scores have key arrhythmia, the less well it is tolerated. Patients common factors that increase the risk of a poor with impaired left ventricular ejection fraction are outcome, including abnormal ECG, age above usually less able to tolerate fast heart rhythms. The 40 years and history of heart failure or myocardial posture of a patient during the onset of the infarction, which highlights the importance of arrhythmia also has an influence on tolerability. structural heart disease in the prognosis of syn- Finally, the use of vasoactive drugs may adversely cope. affect the haemodynamic response during tachy- cardia. The initial evaluation is therefore critical in patients with syncope. A clinical history, physical Bradycardia due to sick sinus syndrome or examination and ECG should always be conducted advanced atrioventricular block is another com- if there is suspicion of cardiac syncope. Further mon cause of syncope in patients with heart diagnostic work-up is guided by the findings of the disease. Interruption of cerebral blood flow for initial evaluation.

338 ª 2013 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2013, 273; 336–344 D. O. Arnar Review: Syncope in heart disease

be present intermittently and therefore one ECG History may not be enough to rule them out. Arrhythmo- The evaluation of syncope begins with a thorough genic right ventricular cardiomyopathy is a rela- clinical history. This includes a detailed assess- tively rare disorder with ECG characteristics of T ment of the syncopal event including prodromal wave inversion in the anteroseptal leads and epsi- symptoms and the immediate aftermath. In partic- lon waves. ular patients should be asked how they felt upon awakening after loss of consciousness as this can Blood tests be helpful in differentiating between syncope and other causes of loss of consciousness, such as Whilst blood tests are generally not considered a . The absence of prodromal symptoms can valuable part of the diagnosis of syncope, a com- be consistent with syncope due to arrhythmia, plete blood count and electrolyte levels should be especially bradyarrhythmia. Chest pain, shortness measured in most instances. In selected patients, if of breath and tachypalpitations are also indicative there is suspicion of acute ischaemia or infarction, of cardiac syncope. The observations of witnesses cardiac biomarkers, preferably a troponin, should to the event are often helpful. be evaluated. In some cases, more than one tropo- nin test may be needed to rule out . If a pulmonary embolus is suspected, Physical examination measurement of D-dimer levels may be helpful. Soon after the event, a detailed physical examina- tion should be carried out, including measurement Echocardiogram of (both supine and standing). In particular, the cardiovascular examination should The echocardiogram is a relatively simple noninva- include evaluation of jugular venous distension, sive test that can easily be performed at the bedside, murmurs or additional on cardiac even in the emergency department. This test can and displaced point of maximal provide useful information, especially if structural impulse. Carotid auscultation should also heart disease is suspected or if a patient with known be performed for evaluation of and the quality heart disease presents with syncope. The echocar- of the carotid . Lung auscultation should diogram provides a good estimate of left ventricular determine the presence of rales and the respiratory function, including signs of regional wall motion rate and pattern. The quality of peripheral abnormalities that are consistent with coronary needs to be evaluated. A neurological examination artery disease. In addition, left ventricular size and should be performed to assess any abnormalities of thickness are readily visualized by this technique. cognition, speech, motor strength, sensation or The presence of , including visual fields. aortic stenosis, can be evaluated. Tricuspid regur- gitation, particularly if accompanied by dilatation of the right ventricle, raises suspicion of a pulmonary ECG embolus. Right ventricular dilatation and thinning The 12-lead ECG is an important tool in the initial of the wall may be present in conditions such as evaluation of syncope. The ECG can provide infor- arrhythmogenic right ventricular cardiomyopathy. mation about heart rate and rhythm, and the presence of ongoing ischaemia ( changes or ECG monitoring ST depression) or a new infarction (ST elevation). In addition, the presence of Q waves should be noted Individuals with syncope who have evidence of as an indication of a prior myocardial infarction or structural heart disease are candidates for hospital a myocardial scar. Changes suggestive of left admission for continuous telemetry. Holter moni- might be present on the toring, for 24 h or longer, is frequently used for ECG. The QT interval should be measured and further evaluation of heart rate and rhythm in evaluated for abnormally long or short QT inter- patients with syncope. The implantable loop recor- vals. The presence of a delta wave, Brugada der, a small wireless monitor placed subcutane- pattern, bundle branch block or atrioventricular ously in the chest, is becoming increasingly used conduction abnormalities should also be noted. It for long-term ECG monitoring. Storage of ECG is important to acknowledge that some of the ECG tracings can be activated either by prespecified changes associated with these disorders may only criteria or by the patients during symptoms. This is

ª 2013 The Association for the Publication of the Journal of Internal Medicine 339 Journal of Internal Medicine, 2013, 273; 336–344 D. O. Arnar Review: Syncope in heart disease

a promising tool for use in those with recurrent heart via venous puncture, usually in the groin. syncope of unknown cause [20]. The battery of the Programmed stimulation of the ventricles is used most recent loop recorders can last for up to to evaluate the risk of developing VT [25]. 36 months. It is very important when interpreting Although the induction of monomorphic VT is the results of rhythm monitoring to correlate considered a definite abnormality, the induction of symptoms with the results of the ECG tracings. ventricular fibrillation is nonspecific. Sinus node function and atrioventricular conduction are also tested, but the sensitivity for these abnormalities Syncope in patients with suspected or known coronary artery is poor [26]. Inducibility of VT is associated with a disease high risk of sudden cardiac death whereas non- The presence of ischaemic heart disease increases inducibility predicts a low risk of sudden cardiac the risk of syncope being due to ventricular death [27]. The value of the electrophysiology arrhythmias. This, in particular, applies to indi- study in patients with normal left ventricular viduals with a left ventricular ejection fraction of function and no is rela- less than 35%–40%. The risk of death in patients tively low [28]. with syncope and coronary artery disease is directly proportional to the severity of left ventric- It is worth noting that ICD-treated patients remain ular dysfunction [5]. at risk of syncope because only the risk of sudden cardiac death is being assessed. This implies the The evaluation of patients with syncope who are at need for identification of the precise mechanism of risk of coronary artery disease should include an syncope in these patients and specific treatment if evaluation for myocardial ischaemia as well as for possible [6]. the signs of previous myocardial infarction. The choice of initial tests may vary according to the In patients with coronary artery disease, if the presentation and the level of suspicion of ischae- suspicion of a brady- or tachyarrhythmia is high mia, but might include exercise stress testing or a despite a normal electrophysiological evaluation, myocardial perfusion imaging study. It is notewor- an implantable loop recorder may be considered. thy that syncope can be the only presenting symp- tom of myocardial infarction in elderly patients. Syncope and nonischaemic dilated cardiomyopathy In patients with coronary artery disease and a Nonischaemic dilated cardiomyopathy, where left severely depressed ejection fraction (<35%), who ventricular function is reduced due to reasons present with syncope, the risk of malignant ar- other than as a consequence of coronary artery rhythmias is such that an implantable cardioverter disease, can also be associated with syncope. defibrillator (ICD) may be indicated regardless of Likely causes are ventricular arrhythmias, brad- the perceived aetiology of the event [21]. Even in yarrhythmias and , either the absence of syncope, an ICD has been shown to due to a decreased cardiac output or as a side effect improve mortality in this particular group of of the medications used to treat the dilated cardio- patients [22, 23], and therefore invasive electro- myopathy. Syncope is an ominous sign in this physiology study for risk stratification with regard population; in one series, almost half of the to VT is not required. Such a study can, neverthe- patients presenting with this symptom had died less, help to determine a specific diagnosis, suddenly within 1 year of presentation [29]. It is although in a patient with noninducible arrhyth- interesting that in this same study, 70% of those mias a device is still indicated. On the other hand, who presented with VT or sudden cardiac death if there is a history of coronary artery disease, even had a prior syncopal event. with prior myocardial infarction, but the ejection fraction is preserved (>35%–40%), a cardiac elec- As with ischaemic cardiomyopathy, an ICD is trophysiology study may be indicated for further indicated for those who have an ejection fraction risk stratification. The prognosis of patients with a of less than 35% [21]. However, the data on the normal electrophysiological result, under these mortality benefit of a defibrillator are not as robust circumstances, is favourable [24]. for nonischaemic as for ischaemic cardiomyopa- thy. The DEFINITE trial enrolled only patients with An electrophysiology study is performed by plac- nonischaemic heart failure and, although there ing catheters in the right-sided chambers of the was a significant reduction in sudden death, there

340 ª 2013 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2013, 273; 336–344 D. O. Arnar Review: Syncope in heart disease

was only a borderline significant reduction in tory of resuscitated cardiac arrest, family history overall mortality [30]. of sudden death, nonsustained VT, marked (  30 mm) hypertrophy and decreased blood pres- Invasive electrophysiology assessment is not as sure with exercise [35]. Invasive electrophysiology helpful a risk stratification tool for those with assessment is not particularly helpful for risk nonischaemic cardiomyopathy as for those with stratification of this condition. coronary artery disease. In a small study of patients with nonischaemic cardiomyopathy, Despite the high risk of ventricular arrhythmias in unexplained syncope, a normal electrophysiology hypertrophic cardiomyopathy, syncope in this dis- study, and who were subsequently treated with an order can be caused by a variety of mechanisms. ICD, 50% received appropriate therapy with a Individuals with hypertrophic cardiomyopathy are defibrillator in the first 2 years after implantation at increased risk of atrial fibrillation which can [31]. Thus, the implications of a normal electro- impact the clinical course of the disease [36]. physiology study in patients with nonischaemic Impaired left ventricular relaxation and heart fail- cardiomyopathy are not as clear as for those with ure can result in left atrial enlargement and atrial coronary artery disease and preserved ejection fibrillation. The latter is associated with increased fraction. morbidity and mortality due to loss of active diastolic left ventricular filling and decreased dia- As for patients with ischaemic cardiomyopathy, an stolic filling time with rapid ventricular rates. implantable loop recorder may be considered in Patients with severe obstruction of the left ventric- those with nonischaemic cardiomyopathy in whom ular outflow tract may experience syncope during left ventricular function is relatively preserved exercise. (>35%–40%), when detailed evaluation has not demonstrated abnormalities, but arrhythmias are The main treatment for patients at high risk of still strongly suspected. sudden death is an ICD. This device is recom- mended for patients resuscitated from sudden cardiac death or sustained ventricular tachycar- Syncope in hypertrophic cardiomyopathy dia and is considered a reasonable option if there Hypertrophic cardiomyopathy is a relatively com- is a family history of sudden cardiac death, mon (1 : 500) inherited disease that is caused by maximum wall thickness of  30 mm or recent mutations in genes encoding sarcomere proteins unexplained syncope [35]. In those with nonsu- [32, 33]. There are different forms of hypertrophy of stained VT or an abnormal blood pressure the left ventricle, but asymmetric septal hypertro- response to exercise, an ICD might be useful in phy is the most common. This type involves certain circumstances. Beta blockers are fre- primarily the proximal and mid portion of the quently prescribed and drugs such as amioda- interventricular septum. The disease is suspected rone and disopyramide may also be useful in if the ECG shows signs of hypertrophy with certain situations. inverted T waves in the precordial leads, particu- larly when the degree of myocardial thickness is Arrhythmogenic right ventricular cardiomyopathy and syncope severe. The condition is then confirmed by an imaging study, usually either or Arrhythmogenic right ventricular cardiomyopathy cardiac magnetic resonance imaging (MRI). is a relatively rare disease that is associated with family clustering and characterized by fibrous and In hypertrophic cardiomyopathy, the normal cellu- fatty replacement of the right ventricular myocar- lar architecture is disrupted in the hypertrophied dium [37]. The fatty/fibrous tissue may be a area, and extensive fibrosis (frequently seen as late substrate for ventricular arrhythmias causing syn- gadolinium enhancement on MRI) can increase the cope or even sudden cardiac death. Arrhythmo- risk of malignant ventricular arrhythmias [34]. genic right ventricular cardiomyopathy usually This can lead to syncope or even sudden cardiac affects only the right ventricle although occasion- death. The occurrence of syncope (particularly ally the left ventricle can also be involved. This within the previous 6 months) in hypertrophic condition may be the cause of up to one-fifth of cardiomyopathy is serious and increases the risk sudden deaths in individuals under the age of of sudden cardiac death five-fold [35]. Other risk 35 years [5]. Syncope or sudden death may be the factors for serious arrhythmias include prior his- first manifestation of the disease.

ª 2013 The Association for the Publication of the Journal of Internal Medicine 341 Journal of Internal Medicine, 2013, 273; 336–344 D. O. Arnar Review: Syncope in heart disease

Arrhythmogenic right ventricular cardiomyopathy in the ryanodine receptor in cardiac myocytes. This can be difficult to diagnose and the signs are often defect increases the risk of polymorphic VT during subtle. The ECG may show epsilon waves and exertion or with elevated heart rates [39]. There are inverted T waves in leads V1–V3. An echocardio- no distinct abnormalities on the resting ECG, but gram may show a dilated and thin-walled right polymorphic VT can be seen during an exercise ventricle. A cardiac MRI usually shows right ven- stress test. An ICD is commonly used to treat high- tricular dilatation and fatty/fibrous replacement of risk patients with a primary electrophysiological the ventricle in addition to localized microaneu- disorder. rysm formation. The role of an electrophysiology investigation in arrhythmogenic right ventricular The future: a role for genetics? dysplasia remains unclear. It has been shown that defibrillator therapy can be useful for treatment of Genetic testing for various disorders that can malignant arrhythmias in this condition. cause syncope, including the most common mutations causing LQTS, has become readily available. In addition, tests for mutations associ- Syncope in aortic stenosis ated with Brugada syndrome and catechola- Aortic stenosis is a disorder of calcific degeneration minergic polymorphic VT have become of the aortic valve and, with the ageing of Western commercially available. Testing for sarcomeric populations, has become the most common valvular mutations involved in hypertrophic cardiomyopa- heart disease in Europe. Syncope is usually a sign of thy and desmosomal protein mutations in ar- advanced aortic stenosis. The cause of syncope in rhythmogenic right ventricular cardiomyopathy is patients with advanced aortic stenosis is likely to be also possible. multifactorial. In general, syncope with aortic ste- nosis occurs with exercise. It has been presumed At present, the optimal use of genetic testing in that the reduced degree of valve opening inhibits the patients who have survived a cardiac arrest or had necessary increase in cardiac output whilst periph- a suspected cardiac syncopal event is still unde- eral vascular resistance falls on exertion. Other cided. However, genetic testing has been used proposed mechanisms include a vasodepressor postmortem (molecular autopsy) in cases in which response which is triggered by increased left ven- the apparent cause of sudden death is unknown, tricular pressure during exercise in patients with but a primary arrhythmia suspected based on the aortic stenosis [13, 38]. Although severe aortic clinical circumstances and lack of evidence of stenosis is relatively rare amongst individuals who structural heart disease. Recently, in a large series present with syncope, it is an important potential of unexplained cardiac sudden deaths, genetic diagnosis and usually suspected after clinical testing achieved a diagnosis in 34% of cases that examination including cardiac auscultation. The would otherwise have remained unexplained [40]. diagnosis is confirmed by echocardiography. The The Heart Rhythm Society and the European treatment is, in most cases, valve replacement. Heart Rhythm Association have recently issued an expert consensus statement on the use of genetic testing for and cardiomy- Primary electrophysiological disorders opathies [41]. In this comprehensive document, Although primary electrophysiological disorders the indications for genetic testing for these disor- are not in fact structural heart diseases, they are ders are reviewed. important causes of cardiac syncope, particularly in young individuals. These disorders include the There have been further advances in the under- inherited channelopathies, LQTS, short QT syn- standing of the potential genetic contribution to drome and Brugada syndrome. Whilst they can all common causes of syncope such as sick sinus be diagnosed with an ECG, the findings may be syndrome as well as variants that modulate impor- subtle and dynamic. Pharmacological provocation tant electrophysiological parameters such as heart can be helpful if there is suspicion of or Brugada rate, PR interval and QRS duration [42, 43]. syndrome, but the ECG does not show typical type Whether or how this will influence future 1 changes. approaches to common problems such as syncope remains unclear (Fig. 1), but it is likely that genetic Catecholaminergic polymorphic ventricular tachy- information will play an increasing role in medical cardia is most frequent due to an inherited defect decision making in the coming decades.

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