Emerging Risk Stratification in Syncope

NTRODUCTION

The first Guidelines of European Society of Cardiology (ESC) for the management of syncope, were published in 2001, and later reviewed in 2004 ⁽¹⁾. In March 2008, the ESC Committee for Practice Guidelines considered that there were enough new data to justify production of new guidelines. It recognised the need to produce a comprehensive document that is addressed not only to cardiologists but to all physicians who are interested in the field. In new guidelines two distinct reasons for evaluating patients with syncope were defined: one is to identify the precise cause in order to address an effective mechanism-specific treatment and the other is to identify the specific risk to the patient. At that time there was enough evidence contributing in favour that risk often depends on the underlying disease rather than on the mechanism of syncope itself ⁽²⁾. The aim for new guidelines was to provide sufficient background for physicians to avoid confounding these two vitally important concepts in management of patients with syncope. To achieve this aim a great number of specialists were involved, as either full members of ESC, external contributors or reviewers nominated by international societies of neurology, autonomic disease, internal medicine, emergency medicine, geriatrics and general medicine. In total 76 specialists from different disciplines participated in this project.

DEFINITIONS

Syncope is a transient loss of consciousness (T-LOC) due to transient global cerebral hypoperfusion characterised by rapid onset, short duration and spontaneous complete recovery ⁽²⁾. This definition of syncope differs from others by including the cause of unconsciousness that is transient global cerebral hypoperfusion ^(1,2).

That was why the definition of syncope does not include disorders such as epileptic seizures and stroke or any other status of unconsciousness not related to transient cerebral hypoperfusion. By distinguishing both T-LOC and syncope, the present definition minimises conceptual and diagnostic confusion (Figure 1)

Figure 1.

Context of transient loss of consciousness (T-LOC). SCD = sudden cardiac death. Two decision trees separating T-LOC from other conditions are whether consciousness appears lost or not, and whether the four features defining the presentation of T-LOC (transient, with rapid onset, short duration, and spontaneous recovery) are present.

The term ‘pre-syncope’ or ‘near-syncope’ is used often to describe a state that resembles the prodrome of syncope but which is not followed by LOC; doubts remain as to whether the mechanisms involved are the same as in syncope.

Clinical Development

A sudden cessation of cerebral blood flow for as short as 6–8 s has been shown to be sufficient to cause complete loss of consciousness. Syncope is a common complaint in the emergency department. Most potential causes are benign and self-limited. Although rare, syncope can be associated with significant morbidity and mortality and be relevance of important and only symptom of a life-threatening disease.

The primary aim of the clinician, especially in emergency department, is to assess the risks of the patient with syncope and to clarify whether a life-threatening cause/disease of syncope is present, or not.

Typical syncope is brief. Complete LOC in reflex syncope lasts no longer than 20 s in duration. However, syncope may rarely be longer, even as much as several minutes ⁽⁵⁾. In such cases, the differential diagnosis between syncope and other causes of LOC can be difficult. Recovery from syncope is usually accompanied by almost immediate restoration of appropriate behaviour and orientation. Retrograde amnesia, although believed to be uncommon, may be more frequent than previously thought, particularly in older individuals. Sometimes the post-recovery period may be marked by fatigue ⁽⁵⁾.

In some forms of syncope there may be a prodromal period in which various symptoms (e.g. lightheadedness, nausea, sweating, weakness and visual disturbances) warn that syncope is imminent. Often, however, LOC occurs without warning.

Several disorders may resemble syncope in two different ways (Table 1). In some, consciousness is truly lost, but the mechanism is something other than global cerebral hypoperfusion. In other disorders, consciousness is only apparently lost.

Table 1.

Conditions incorrectly diagnosed as syncope

Disorders with partial or complete LOC but without global cerebral hypoperfusion

Epilepsy Metabolic disorders like hypoglycemia, hypoxia, hypocapnia Intoxication Vertebrobasilar TIA

Disorders without impairment of consciousness

Cataplexy Drop attacks Falls Psychogenic pseudosyncope TAI of carotid origin

LOC = loss of consciousness; TIA = transient ischaemic attack.

Classifications and Pathophysiology

Table 2 provides a pathophysiological classification of the principal causes of syncope.

Table 2.

Classification of syncope

AFFERENT PATHWAY	EFFERENT PATHWAY
Reflex syncope (neurally-mediated)
Vasovagal: Mediated by emotional distress: fear, pain, instrumentation, blood phobia Mediated by orthostatic stress	Both vasomotor and cardio- inhibitory mechanisms are present. Arterial Hypotension the causes global cerebral hypoperfusion is result of both decrease in cardiac output and drop of peripheral vas- cular resistance.
Situational: Cough, sneeze Gastrointestinal stimulation: swallow, defecation, visceral pain Post - micturition Post - exercise Post – prandial Others e.g. – laugh, brass instrument playing, weightlifting
Carotid sinus syncope: Typical form/presentation Atypical form/presentation with or without apparent trigger
Syncope due to orthostatic hypotension
Primary autonomic failure: Pure autonomic failure Multiple system atrophy Parkinson’s disease Lewy body dementio	Global cerebral hypo- perfusion is mainly due to drop of periph- eral vascular resistance. Often accom- panying also with a small decrease in cardiac output.
Secondary autonomic failure: Diabetes Amyloidosis Uraemia Spinal cord injuries
Drug-induced orthostatic hypotension: Alcohol Vasodilators Diuretics Phenotiazines Antidepressants
Volume depletion: Haemorrhage Diarrhea Vomiting, etc
Cardiac syncope (due to cardiovascular cause)
Arrhythmia as primary cause: Sinus node dysfunction and bradycardia/tachycardia syndrome Atrioventricular conduction system disease or blockade Implanted device malfunction	Global cerebral hypo- perfusion is mainly due to decrease in car- diac output. May or may not be accompanying by mild drop of periph- eral vascular resistance.
Tachycardia: Supraventricular Ventricular
Drug induced: Bradycardia Tachyarrhythmia
Structural heart disease: Valvular heart disease or prosthetic valve disfunction Acute myocardial ischemia Hypertrophic cardiomyopathy Cardiac masses (myxoma, tumors) Pericardial disease/tamponade Congenital anomaly of coronary arteries
Other Structural diseases: Pulmonary hypertension Pulmonary embolism Aortic dissection

Experience from tilt testing showed that a decrease in systolic BP to 60 mmHg or lower is associated with syncope ⁽⁶⁾. Systemic BP is determined by cardiac output (CO) and total peripheral vascular resistance, and a fall in either can cause syncope, but a combination of both mechanisms is often present, even if their relative contributions vary considerably. However the main tree pathophysiological types of syncope described in Table-1 can be schematically assorted by their relation to low cardiac output and/or low peripheral resistance (see Figure 2).

Figure 2.

Pathophysiological basis of the classification of syncope. OPT = output; RST = resistance; BP = blood pressure

Reflex Syncope (neurally mediated syncope)

Reflex syncope may also be classified based on its trigger (afferent pathway) or based on the efferent pathway most involved (Table 2). The term ‘vasodepressor type’ is commonly used if hypotension, due to a drop of peripheral vascular resistance, predominates. ‘Cardioinhibitory’ is used when bradycardia or asystole predominate, and ‘mixed’ is used if both mechanisms are present. It must be recognised that this is a simplification, because many different mechanisms can be present in the context of a specific situation, such as micturition or defecation syncope. The triggering situations vary considerably in and between individual patients.

In most cases the efferent pathway does not depend strongly on the nature of the trigger (afferent pathway). For example, micturition syncope may present as cardioinhibitory or vasodepressor syncope in different patients. Knowing the various triggers is clinically important, as recognising them may be crucial in diagnosing syncope:

‘Vasovagal’ syncope (VVS), also known as the ‘common faint’, is mediated by emotion or by orthostatic stress. It is usually preceded by prodromal symptoms of autonomic activation (sweating, pallor, nausea). It is the most common cause of syncope, accounting for 25 to 65 percent of cases ⁽⁷⁾.

‘Situational’ syncope traditionally refers to reflex syncope associated with some specific circumstances. Post-exercise syncope can occur in young athletes as a form of reflex syncope as well as in middle-aged and elderly subjects as an early manifestation of autonomic nervous failure (ANF) before they experience typical orthostatic hypotension (OH).

‘Carotid sinus’ syncope is rare spontaneous form it is triggered by mechanical manipulation of the carotid sinuses ⁽⁸⁾. In the more common form no mechanical trigger is found and it is diagnosed by carotid sinus massage (CSM)

Patients diagnosed with neurally mediated syncope have an excellent prognosis with no increase in mortality or morbidity ⁽⁹⁾. However, in patients with severe valvular heart disease and hypertrophy of cardiac muscle neurally mediated syncope should be taken in account as a warning for high risk ⁽²⁾.

Orthostatic Hypotension (orthostatic intolerance syndromes)

In contrast to reflex syncope, in ANF sympathetic efferent activity is chronically impaired so that vasoconstriction is deficient. Upon standing, BP falls and syncope or pre-syncope occurs. OH is defined as an abnormal decrease in systolic BP upon standing.

Strictly from a pathophysiological point of view there is no overlap between reflex syncope and ANF, but the clinical manifestations of the two conditions frequently overlap, sometimes making differential diagnosis difficult. ‘Orthostatic intolerance’ refers to symptoms and signs in the upright position.

OH comprises between five and 24 per cent of syncope cases and can be defined by a drop in blood pressure of more than 20 mmHg, or a reflex tachycardia of more that 20 beats per minute. It can be due to primary and secondary autonomic failure (Table 1). Acute severe haemorrhage can manifest as syncope. Important potential causes include: trauma, gastrointestinal bleeding, ruptured aortic aneurysm, ruptured ovarian cyst, ruptured ectopic pregnancy, and ruptured spleen. Haemodynamically significant pulmonary embolism is an uncommon but well documented cause of syncope.

‘Classical OH’ is a physical sign defined as a decrease in systolic BP ≥20 mmHg and in diastolic BP ≥10 mmHg within 3 min of standing, described in patients with pure ANF, hypovolemia or other forms of ANF.

‘Initial OH’ is characterised by a BP decrease immediately on standing of >40 mmHg.13 BP then spontaneously and rapidly returns to normal, so the period of hypotension and symptoms is short.

‘Delayed (progressive) OH’ is common in elderly persons. It is attributed to age-related impairment of compensatory reflexes and stiffer hearts in the elderly sensitive to a decrease in preload. Delayed OH is characterised by a slow progressive decrease in systolic BP on assuming erect posture. The absence of a bradycardiac reflex (vagal) differentiates delayed OH from reflex syncope. Delayed OH may, however, be followed by reflex bradycardia.

‘Postural orthostatic tachycardia syndrome’ (POTS). Some patients, mostly young women, present with severe complaints of orthostatic intolerance, but not syncope, with very marked heart rate (HR) increases (>30 beats per minute (b.p.m.) or to >120 b.p.m.) and instability of BP. POTS is frequently associated with chronic fatigue syndrome. The underlying pathophysiology is unknown.

Cardiac Syncope (cardiovascular)

Arrhythmias are the most common cardiac causes of syncope. They induce haemodynamic impairment, which can cause a critical decrease in cardiac output (CO) and cause global cerebral hypoperfusion. However syncope often has multiple contributory factors, including heart rate, mechanism of arrhythmia, baseline left ventricular function, posture and adequacy of vascular compensation. Regardless of such contributing effects, when an arrhythmia is the primary cause of syncope, it should be specifically treated.

In intrinsic sick sinus syndrome, the sinoatrial node is damaged, because of either abnormal automaticity or sinoatrial conduction abnormalities. In this situation syncope is due to long pauses caused by sinus arrest or sinoatrial block and a failure of escape mechanism. These pauses are most frequently encountered when an atrial tachyarrhythmia suddenly stops (brady-tachy syndrome).

Mobitz II block, ‘high grade’, and complete AV block are frequently related to syncope. In these cases, the cardiac rhythm may become dependent on subsidiary or escape pacemaker sites that are often unreliable. Syncope occurs because the delay before these pacemakers begin to ‘fire’ is long. In addition these subsidiary pacemaker sites typically have relatively slow rates (25–40 b.p.m.). Bradycardia also prolongs repolarisation and predisposes to polymorphic ventricular tachycardia (VT), especially of the torsade de pointes type ⁽¹⁰⁾.

Syncope or near-syncope occurs at the onset of paroxysmal tachycardia, before vascular compensation develops. Almost 20% of patients have syncope or near-syncope at the time of first episode of atrial fibrillation. In such cases consciousness is, in general, restored before tachycardia terminates. In case of more serious arrhythmias, when haemodynamics remain inadequate due to tachycardia, unconsciousness is maintained. Recovery is then not spontaneous and it cannot be classified as syncope, and constitutes cardiac arrest or aborted sudden cardiac death.

Several drugs can cause brady- and tachyarrhythmias. Many antiarrhythmic drugs can cause bradycardia as a consequence of their specific effect on sinus node function or AV conduction. Syncope due to torsade de pointes is not uncommon, especially in women, and is caused by drugs prolonging the QT interval. It is particularly frequent in patients affected by the long QT syndrome. QT-prolonging drugs belong to different categories, i.e. antiarrhythmics, vasodilators, psychotropics, antimicrobials, non-sedating antihistamines, etc. (www.qtdrugs.org).

Patients with cardiac syncope are at significant risk for sudden death ⁽¹⁰⁾. Patients with syncope and a history of congestive heart failure are at even greater risk ⁽¹¹⁾.

Structural cardiovascular diseases can cause syncope when circulatory demands outweigh the impaired ability of the heart to increase its output Table 2 Syncope is of great concern when it is associated with conditions in which there is fixed or dynamic obstruction to left ventricular outflow. Syncope in structural heart diseases is not solely based on mechanical obstruction, but may be in part due to inappropriate reflex vasodilation and/or primary cardiac arrhythmia. Furthermore, arrhythmias, particularly atrial fibrillation, are frequently important causes of faint. Thus, the mechanism of syncope may be multifactor. To recognise the heart as the cause of the problem is justified by the need to correct the underlying structural heart disease.

Conditions Incorrectly Diagnosed as Syncope

Non Syncopal Neurologic Conditions Mimic Syncope are rare. Examples of neurologic syncope include: subarachnoid hemorrhage, transient ischemic attack, subclavian steal syndrome and complex migraine headache. Stroke and transient ischemic attacks generally cause focal neurologic deficits that do not recover rapidly or completely. Patients presenting with syncope following a headache require evaluation for a possible subarachnoid haemorrhage.

Patients with psychiatric syncope are generally young, without cardiac disease, and complain of multiple episodes. Anxiety and panic disorders can cause situational syncope. Emergency clinicians must be cautious when attributing syncope to psychiatric causes.

Metabolic conditions mimicking syncope include hypoglycemia and hypoxia.

Epidemiology

There is a very high prevalence of first faints in patients between 10 and 30 years, with a peak of - 47% in females and 31% in males around the age of 15. In the Framingham study the incidence of syncope shows a sharp rise after the age of 70 years.

A very small fraction of patients with syncope in the general population, present in any clinical setting. In the Framingham offspring study, 44% of the participants with an episode of LOC reported that they did not seek medical advice ⁽¹²⁾. The proportion of patients not seeking medical evaluation in the younger population is higher compared to middle-age population.

Reflex syncope is the most frequent cause of syncope in any setting. Syncope secondary to cardiovascular disease is the second most common cause. In patients younger than 40 years OH is a rare cause of syncope; OH is frequent in very old patients. While in the young reflex syncope is by far the most frequent cause of T-LOC, in the elderly multiple causes are often present and the medical history may be less reliable than in the young. ^(13,14)

Evaluation and Risk Stratification in Syncope

With regard to syncope associated risk stratification, two important items should be considered: (a) risk of death and life-threatening events; and (b) risk of recurrence of syncope and physical injury. Although there is a risk for harm for patient and surroundings associated with short lost of consciousness, but it seems to be low ⁽²⁾.

Structural heart disease and primary electrical disease are major risk factors for sudden cardiac death (SCD) and overall mortality in patients with syncope. Even benign syncope like reflex or OH is associated with at least 2-fold higher risk of death when ether structural heart disease or primary electrical disease is found. Conversely, young patients in whom structural or electrical heart disease have been excluded and are affected by reflex syncope have an excellent prognosis ⁽¹²⁾.

Poor outcomes seem to be related to the severity of the underlying disease rather than to syncope per se. Several clinical factors able to predict outcome have been identified in some prospective population studies involving a validation cohort. Outcome predictors from several different studies that have analysed the impact of different clinical data on the follow-up of patients presenting with are summarised in Table 3. Overall, the presence of abnormal ECG, severe palpitation preceding syncope, syncope during effort, history of ventricular arrhythmia, age between 45 and 65 or data suggestive of cardiovascular disease predict worse prognosis at 1–2 years of follow-up ^(15-18).

Table 3.

Risk stratification at initial evaluation in prospective population studies including a validation cohort

RISK FACTOR	POINT SCORE	One year total mortality or cardiac syncope (if otherwise not specified) associated with single point	Reference Source
Palpitation before syncope	3 +	5 – 8 % (for up to 2 years)	17
Syncope during effort	2 or 3	4 – 8 % (for up to 2 years)	17
Abnormal ECG	1 or 2	3 – 8 %	15-18
History of ventricular arrhythmia	1	3 – 8 %	15
Age > 45	1	3 – 6 %	15
Known Heart Disease	1 or 2	1 – 6 %	16;17
Known Cardiovascular Disease	1 or 2	1 – 5 %	16
History of CHF	1	1 – 5 % up to 2 years	17
Syncope while supine	1 or 2	1 – 2 % up to 2 years	17
Age > 65	1	0 – 2 %	16
Lack of prodrome	1	0 – 2 %	16
CHF at evaluation	0 or 1	High probability of serious event at 7 days	18
Shortness of Breath	0 or 1	High probability of serious event at 7 days	18
Haematocrit < 30 %	0 or 1	High probability of serious event at 7 days	18
Systolic BP < 90 mmHg	0 or 1	High probability of serious event at 7 days	18

ECG = electrocardiogram

A combination of historical features, physical examination and ECG findings can identify a life-threatening cause of syncope.

The initial evaluation should answer three key questions:

1. Is it a syncopal episode or not?

2. Has the etiological diagnosis been determined?

3. Are there data suggestive of a high risk of cardiovascular events or death?

History and Clinical Evaluation

The differentiation between syncope and non-syncopal conditions with real or apparent LOC can be achieved in most cases with a detailed clinical history only ⁽¹⁹⁾ but sometimes can be extremely difficult.

The following questions should be answered:

1. Was LOC complete?

2. Was LOC transient with rapid onset and short duration?

3. Did the patient recover spontaneously, completely?

4. Did the patient lose postural tone?

If the answers to all these questions are positive, the episode has a high likelihood of being syncope. If the answer to one or more of these questions is negative, exclude other forms of LOC before proceeding with syncope evaluation.

Initial evaluation is able to define the cause of syncope in 23–50% of patients ⁽¹⁹⁾ Table 4 lists some of the most important questions that must be answered when taking the clinical history of patients with syncope.

Table 4.

Important historical features

Questions regarding the circumstances just preceding the syncope

Position (supine, sitting, standing) Activity (exercising, or just after exertion, during or after urination, defecation, swallowing etc.) Condition (warm or hot place, crowded, prolonged standing, post-prandial period) Precipitating events (like fear, pain, neck movement)

Questions regarding the onset of syncope

Nausea, vomiting, abdominal discomfort, filling of cold, sweating, aura, pain in neck or shoulders, blurred vision, dizziness Palpitation

Questions to eyewitnesses*

Way of falling (slumping or kneeling over), Skin colour (pallor, cyanosis, flushing) Duration of LOC Breathing pattern (snoring) Movements (tonic/clonic, automatism, duration or movements, onset in relation to LOC/fall, tongue biting)

Questions regarding the end of attack (if needed patients answers can be compared with those of eyewitnesses)*

Nausea, vomiting, sweating, urinary or defecation, confused consciousness, muscle aches, injury, chest pain, palpitation

Background check

Family history of SCD Known cardiac disease or arrhythmia Known neurological disease Metabolic disorder or disease Previous syncope or equivalent, frequency, conditions/similarity Exposition to drugs or toxin

^*Vital signs during and immediately after the event should be noted when available.

There are some findings in the clinical history, physical examination or ECG that can be considered diagnostic of the cause of syncope, permitting no further evaluation and institution of treatment (see Table 5). In many other situations, the findings of initial evaluation do not permit a definite diagnosis to be made, but suggest some causes. In these cases, additional testing is usually needed.

Table 5.

Clinical features that can suggest a diagnosis on initial evaluation

Reflex Syncope (neurally mediated)
No heart disease Long history of recurrent syncope After sudden unexpected/unpleasant sight, sound, smell or pain Prolonged standing Crowded hot places Nausea, vomiting associated with syncope During the meal or post-prandial Head rotation or pressure in carotid sinus (tumours, shaving tight collars ) After exertion	Neurally mediated Low risk syncope
Syncope due to OH
After standing up (quick change from supine to stand) Use/start/change in dose of drugs that can lower BP Sanding after exertion Prolonged sanding in crowded/hot places Presence of autonomic neuropathy or Parkinson’s disease	Sadden drop of peripheral vascular refractory Low risk syncope
Cardiac Syncope (due to cardiovascular disease)
Presence of structural heart disease Family history of SCD or chanelopathy During exertion At supine position Sadden onset of palpitation just before LOC Abnormal ECG (the following findings are suggestive for cardiac syncope) - bifascicular block (QRS duration over 120 msec) - Second degree AV block (any type) - Sinus bradycardia (< 50 BPM) even without symptoms - Sinus pauses > 3 second - Non-sustained VT - Pre-excited QRS complexes - Long or short QT intervals - RBBB pattern with ST elevation in V1-V3 (suggestive for Brugada syndrome) - Negative T waves in V2-V3 or even further (suggestive for ARVC) - Epsilon waves in V1 (suggestive for ARVC) - Q wave suggesting MI	High risk syncope Refer for further evaluation

ARVC = arrhythmogenic right ventricular cardiomyopathy; AV = atrioventricular; LBBB = left bundle branch block; OH = orthostatic hypotension; RBBB = right bundle branch block; VT = ventricular tachycardia. MI = myocardial infarction; BPM = beat per minute; msec = milliseconds

A careful history is often the most useful tool for identifying an etiology and directing further evaluation of a syncopal event. The prolonged upright posture, a trigger for the event was associated with vasovagal etiology, meanwhile exercise-related syncope associated with cardiac etiology ⁽⁷⁾. Some triggers are associated with specific primary electrical disturbances.

As an example, for patients with long QT syndrome, the triggers for the most common genotypes are acute arousal (or startle) and auditory stimuli ⁽²⁰⁾. Children with familial catecholaminergic polymorphic ventricular tachycardia can develop arrhythmias in association with emotional or physical stress.

A description of the event should include the report of symptoms prior to the onset of syncope, as well as the witness’s description of the syncopal event itself like described in Table 4.

For example, let us discuss breathing patterns from Table 4: a history of an abnormal respiratory pattern prior to the syncopal episode in children suggests hyperventilation or breath holding as the etiology. Patients with hyperventilation are frequently adolescents experiencing some type of emotional stress. They may describe additional symptoms such as chest pain, lightheadedness, paresthesias and visual disturbances. Breath holding spells occur in younger children (typically 6 to 24 months of age) usually during prolonged cry.

A cardiac evaluation is indicated for children with a family history of syncope or sudden death or with episodes that are prolonged, frequent or precipitated by startle or other nontraumatic stimuli.

Patients with syncope related to hysteria (somatisation disorder) or a conversion disorder are commonly adolescents. Expected physiologic signs (such as sweating, pallor or changes in heart rate and blood pressure) are often absent. In addition, during detailed history taking patients may disclose details of the event that clearly indicate no loss of consciousness.

Patients who engage in the choking game purposely attempt self-strangulation or allow strangulation by another person with the hands or a ligature to produce a euphoric state caused by cerebral hypoxia. The plan is to release the pressure just before loss of consciousness, but failure to do so can result in death, particularly when the game is played alone using ligatures.

Position

Patients who lose consciousness with prolonged standing (ie, minimum of 15 to 20 minutes) are more likely to have reflex syncope. Patients who lose consciousness while moving from a lying to a standing position are more likely to have OH. Syncope while sitting or supine is suspicious for arrhythmia ⁽²¹⁾.

Onset

Sudden loss of consciousness without warning or prodrome suggests arrhythmia. Syncope with exertion raises the possibility of arrhythmia or cardiac outflow obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy or pericardial tamponade). These patients warrant a thorough cardiac evaluation, including chest x-ray, electrocardiogram and echocardiography.

Patients with neurocardiogenic (vasovagal) syncope frequently report symptoms before the event that include dizziness, lightheadedness, sweating, nausea, weakness and visual changes (blurred vision, slow visual loss).

Shortness of breath, chest pain or palpitations prior to or during the event are concerning for a cardiac etiology and arrhythmia. Children under 12 often describe sudden onset of sever palpitation as “chest pain”. In these cases electrocardiographic monitoring is recommended (non-invasive and invasive).

Abnormal motor activity (such as tonic-clonic movement or posturing) can occur at the end of LOC, particularly with an arrhythmia. The duration of such activity is usually brief and recovery is rapid. In comparison, prolonged motor activity and/or recovery time are consistent with a seizure ⁽²²⁾. Motor activity in seizure starts almost with LOC.

Seizure versus syncope

Very often clinicians have difficulty determining whether their patient suffered a seizure or syncope. Patients with certain seizure disorders do not manifest generalised convulsions; patients with syncope may have brief tonic and/or clonic episodes. Approximately five to 15 per cent of patients thought to have syncope have a seizure disorder ⁽²³⁾. Factors suggestive of seizure include:

• Prodrome (aura) different from that described for vasodepressor syncope;

• episode of abrupt onset associated with injury;

• presence of a tonic phase before the onset of rhythmic clonic activity;

• head deviation or unusual posturing during the episode;

• tongue biting (particularly involving the lateral aspect of the tongue);

• loss of bladder or bowel control;

• prolonged post-event (postictal) phase during which patient’s conscience is confused and disoriented

Medical History

A past medical history of congenital heart disease (corrected or uncorrected) or arrhythmia should immediately focus attention on a potentially serious cardiac etiology. Numerous previous syncopal events suggestive for reflex or OH related event or maybe psychogenic cause. Cardiac etiology is less common in such a case.

During history taking it is important to pay attention to other significant medical problems (such as diabetes), to menstrual history, recent changes in medication, access to medications or illicit drugs.

Medications

The effects of medications account for five to 15 per cent of syncopal events. The mechanism can be orthostasis or cardiotoxicity. Medications often implicated include calcium channel blockers, beta blockers, alpha blockers, nitrates, antiarrhythmics, diuretics (affecting volume status and electrolyte concentrations) and medications affecting the QTc interval ⁽²⁴⁾.

Family history

A family history of early cardiac death (less than 45 years of age), sudden deaths including unexplained accidents involving a single motor vehicle or drowning, known arrhythmia (long QT syndrome), and familial cardiomyopathy increase the concern for a possible cardiac etiology ⁽²⁵⁾. Usually question like “Do you have sudden deaths in family?” dos not yield much. Careful family tree drawing is recommended in suspicious cases.

At the same time a family history of reflex syncope or OH fainting may be present in up to 90 per cent of children with these conditions ⁽²²⁾.

Physical examination

A complete physical examination should be performed, including vital signs (with orthostatic pulse and blood pressure measurements) and cardiac and neurologic examinations.

Measurements of blood pressure and heart rate to identify orthostatic hypotension should be taken while the patient is sitting, then after standing for two minutes. Abnormal values include a decrease in systolic blood pressure more than 20 mmHg or an increase in heart rate more than 20 beats per minute from sitting to standing. Clinicians should keep in mind that syncope from orthostatic hypotension is a diagnosis of exclusion in the emergency department, reserved for low risk patients who have symptoms consistent with the diagnosis. Percutoral evaluation of heart borders is necessary in selected cases. Signs of congestive heart failure such as swelling of lower extremities and palpator hepatomegaly are consistent with cardiac disease.

Cardiac auscultation can reveal the characteristic findings for structural heart disease: aortic stenosis presents with systolic ejection murmur and ejection click, the classic murmur of hypertrophic cardiomyopathy is an outflow murmur that decreases in intensity with increased venous return to the heart (during a valsalva manoeuver or squatting).

Signs of congestive heart failure such as rales, a gallop - 3rd heart sound or even 4th heart sound are often findings in patients with cardiac disease.

Neurologic status evaluation

Patients who were unconscious for more than several seconds should be evaluated for a neurologic disorder, such as a seizure or migraine syndrome. An age appropriate neurologic exam should be performed to identify focal deficits. In the patient with prolonged loss of consciousness, seizure activity a routine outpatient EEG should be considered. Neuroimaging may be indicated emergently for patients with focal neurologic deficits, persistently altered mental status, sever head each that started prior and continues after the event, or a significant head injury as the result of the syncopal episode ⁽²⁾.

Special exams: ECG

ECG is a standard part of the syncope work up, despite its low diagnostic yield ⁽²⁶⁾ it reminds widely accessible, reliable, inexpensive and quick risk-stratification toll. ECG findings that should be noted include:

• nonsinus rhythms (abnormal P wave axes);

• excessive bradycardia usually HR lower than 50;

• atrioventricular block (more P waves than QRS complexes on the ECG);

• signs of myocardial injury (QT elevation or depression or abnormally big or invert T waves). A pattern of myocardial injury may be seen with congenital coronary artery abnormalities;

• prolonged QT interval (in any case when the end of T wave is close to the middle of RR interval or even “crossing” it on any of 12 leads);

• short R to P interval with signs of ventricular preexcitation (WPW syndrome, palpitations in history);

• signs of left ventricular hypertrophy (LVH) or strain (leftward axes and no decrease in R waves voltage from V4 to V6) are consistent with hypertrophic cardiomyopathy. However normal ECG do not exclude LVH and ECHO cardiography indicated in selected cases with high suspicion for LVH;

• any case with QRS wider than 120 msec has conduction abnormality in the ventricle(s) and should be referred for through cardiac examination;

• epsilon and inverted T waves on V1-V3 or in some sever cases even in V4 and V5 may be present in patients with ARVC;

• ARVC believed to be inheritance disease related to more than five known mutations. It is a progressive disorder. However, ECG-bent phenotype-penetrations mentioned above may not be present in all types of the disease, especially in young patients

Special exams

Laboratory tests. Most patients present for evaluation hours to days after the event has occurred. In the asymptomatic patient, extensive laboratory blood work such as serum glucose, electrolytes, and complete blood counts are rarely helpful. A bedside glucose determination immediately after the episode, hematocrit for patients who are at risk for anaemia, coagulation studies, a urine pregnancy test in post menopausal females and urine toxicology screen for drug-abuse in patients with altered metal status may be helpful in some situations. A hematocrit less than 30 increases the risk of adverse short-term events in patients with syncope ⁽¹⁸⁾.

Special exams: emergent ECHO cardiography

Emergent echocardiography should be reserved for those patients with strongly suspected cardiac etiology due to the presence of an abnormal ECG, pathologic murmur, history of cardiac disease, suspicious for tamponade or exercise-induced syncope ⁽²⁷⁾.

Injury assessment and general examination

The emergency clinician should perform a head to toe exam looking for evidence of trauma. Common injuries associated with falls following syncope include facial fractures, hips fractures, wrist fractures and subdural haematomas.

Patients who may require a more extensive cardiac evaluation (such additional ECG monitoring, a stress test or tilt test) can generally be referred for an outpatient evaluation.

Indications For Referral Or Admission

The patients with concerning features such as absence of a significant prodrome, associated palpitations or chest pain, a family history of syncope or sudden death, or recurrent episodes should be referred for further cardiac evaluation.

Follow-up consultation with a neurologist should be considered for patients with prolonged loss of consciousness and/or a history of focal neurologic abnormalities that have resolved. Patients with confused consciousness after event also need further neurologic assessment.

Admission to the hospital for further evaluation and observation should be considered under the following circumstances: evidence of cardiovascular disease (such as heart failure or arrhythmia); an abnormal ECG; chest pain with syncope, syncope with cyanosis, apneal or bradycardia spells that resolve only with vigorous stimulation, abnormal neurologic findings, orthostatic hypotension that does not resolve with fluid therapy.

Patients suspicious for drag-abuse or intoxication should be also admitted to the hospital for monitoring and treatment. Children with known congenital heart disease may have abnormalities consistent with their diagnosis and/or surgical repair. Findings such as a systolic ejection murmur with ejection click (valvular aortic stenosis) or an outflow murmur that decreases in intensity with increased venous return to the heart (hypertrophic cardiomyopathy) may indicate undiagnosed structural heart disease.

In 2007 The American College of Emergency Physicians (ACEP) published evidence-based guidelines on the management and disposition of patients with syncope ⁽²⁸⁾.

According to that guideline high-risk patients should be investigated in the Emergency Department (ED) and likely admitted. Low-risk asymptomatic patients may be discharged and provided outpatient follow-up can be arranged. Use of history and physical examination to detect CHF, and a 12-lead ECG are very important for patients with syncope. The ACEP document contains two important caveats: Associated symptoms suggestive of an underlying disease process should be actively pursued (e.g., syncope with headache or a new neurologic finding suggesting subarachnoid haemorrhage), and the guidelines exclude patients with obvious signs of illness for which syncope is part of the presenting symptom complex.

According to ESC 2009 guideline for syncope ⁽²⁾ short–term high risk criteria which require prompt hospitalisation or intensive evaluation are:

• Severe structural or coronary artery disease (heart failure, low left ventricular ejection fraction, previous MI);

• Clinical or ECG features suggesting arrhythmic syncope;

  • Syncope during exertion or supine;
  • Palpitation at the time of syncope;
  • Family history of SCD;
  • Non-sustained VT;
  • Bifascicular block or other intraventricular conduction abnormalities with QRS duration > 120ms;
  • Inadequate sinus bradycardia (<50 bmp) or sinoatrial block in absence of negative chronotropic medications or physical training;
  • Pre-excited QRS complex;
  • Prolonged or short QT interval;
  • RBBB pattern with ST-elevation in leads V1-V3 (Brugada patterns)
  • Negative T waves in right precordial leads, epsilon waves and ventricular late potentials suggestive of ARVC;

• Important co-morbidities

  • Severe anemia;
  • Electrolyte disturbance.

Normal cardiac examination. Patients with a normal ECG and cardiac examination are unlikely to have a cardiac etiology for their syncopal episode. However, patients with worrisome historical features may require further evaluation as many patients with different chanelopathy or cardiomyopathy were thought as “normal” in terms of cardiac examination before disclosure of gen mutation and its foenotipical penetrations. Many known serious cardiomy-opathies up-to-day can be recognised by only a tiny changes on 12 lead ECG or by special high-resolution imaging tools.

CONCLUSION

In the emergent evaluation of patients with syncope, a diagnosis of reflex (neuraly mediated or vasovagal) syncope is typically a diagnosis of exclusion. Patients with consistent clinical features, such as patients with precipitating events, trauma or with known heart disease should be hospitalised or referred to specialist clinics. Initial clinical evaluation is crucial in the approach to patients with syncope and all patients at ED should have detailed and through history taking, including past medical history and recent event. Physical examination shell includes heart auscultation, palpation and neurological exam. 12-lead ECG evaluation in regards to known risk-factors should be made in all patients at ED. Emergency imaging may be necessary in selected cases. Cardiac evaluation is recommended in those patients with structural heart disease or an abnormal ECG.