Chapter 48 Syncope
Introduction
Syncope is a transient loss of consciousness (TLOC) with subsequent complete resolution and no focal neurologic deficits; it results from cerebral hypoperfusion and does not require specific resuscitative measures. Recent expert consensus conferences, position papers, and narrative reviews have covered the various aspects of syncopal syndromes.1–9
Epidemiology
Approximately 40% of people faint at least once in their lives, and at least 20% of adults faint more than once.10 (Many terms are used by patients to report syncope, such as faint, blackout, and funny spell. To avoid contributing to this plethora of miscommunication, this chapter uses faint and syncope interchangeably.) Syncope comprises 1% to 6% of emergency department (ED) visits, and most patients are admitted to the hospital largely because of diagnostic uncertainty and concern that an underlying cause might result in morbidity or death.11–32 People who faint often present first in their teens and twenties and may faint sporadically for decades.10 This long, usually benign, sporadic history can make for difficult decisions about therapy. An early peak incidence occurs at approximately 15 years for young women; a later important rise in incidence occurs in both sexes after age 65 years.4 Although many patients of all ages experience simple vasovagal syncope, clinicians need to remain vigilant and look for other causes, including sick sinus syndrome, a variety of tachyarrhythmias, carotid sinus syncope, valvular and structural heart disease, and orthostatic hypotension.1–46
Impact on the Health Care System
Although syncope accounts for approximately 1% of ED visits, most patients with syncope with otherwise unknown causes in the community and approximately 45% of syncope patients who present to EDs in North America and Europe experience simple vasovagal syncope. In the United States, approximately $2.4 billion is spent yearly in hospitals to treat syncope.6 In The Netherlands, among those younger than 65 years, 3.8 and 8.5 visits per 1000 person-years are made to family doctors for males and females, respectively.12 Canadian and Italian estimates for ED presentations are 2.5-fold and 3.5-fold higher, respectively, than the estimates from The Netherlands.6 The estimated direct impact on U.S. health care is $2.5 to $10 billion annually.4–6,33,34
Differential Diagnosis of Syncope
Transient Loss of Consciousness
Patients usually present with a history of TLOC, and although most of these patients experience syncope, the differential diagnosis of TLOC should be considered early in assessment. Other causes of apparent TLOC include epileptic and nonepileptic seizures, cataplexy, narcolepsy, pseudo-syncope, and rarer causes such as drop attacks and nonconvulsive epilepsy. The problem faced by assessing physicians is that patients may present simply with a history of unexplained losses of consciousness. The first step is to determine whether the loss of consciousness occurred because of syncope. The most common confusing presentations are addressed in this section. Not all these cause true loss of consciousness, but they can mimic it and therefore must be considered, albeit briefly.1,4
Convulsions and Syncope
Although patients experiencing syncope usually lose motor control and are flaccid while unconscious, they frequently present with a history of convulsions and syncope (Table 48-1).7,9 This raises the question of whether the patients have true epileptic convulsions or convulsions secondary to cerebral hypoperfusion. Stiffness and myoclonic jerking are not uncommon in the latter case and cause confusion in the minds of those who witness the episode. Convulsive syncope can usually be distinguished from epileptic seizures through careful history taking. Stiffness and myoclonus last only a few seconds; only rarely will these patients have a true generalized convulsion. Patients with convulsive syncope usually have a history of recurrent syncope and presyncope. It is often helpful to elicit a similar history of the characteristic presyncopal prodrome of the patient and the symptoms preceding the apparent convulsion. Convulsive syncope rarely occurs when the patient is in the supine position and is usually brief, lasting only a few seconds. Pallor usually accompanies vasovagal syncope, whereas cardiac syncope and epileptic seizures are often accompanied by cyanosis. Myoclonic tremors usually have a fine amplitude, and epileptic seizures usually have dramatically coarse movements. Tongue biting rarely occurs in convulsive syncope and usually involves the tip of the tongue rather than the lateral tongue, as seen in true epileptic seizures. After a syncopal episode, the patient is briefly dazed, but the condition clears within a minute, whereas epileptic seizures can be followed by confusion that can last hours. If a history does not provide a clear conclusion, further testing is warranted.
Table 48-1 Diagnostic Questions to Determine Whether Loss of Consciousness Is Due to Seizures or Syncope
| QUESTION | POINTS (IF YES) |
|---|---|
| At times, do you wake with a bitten tongue after your spells? | 2 |
| At times, do you have a sense of déjà vu or jamais vu before your spells? | 1 |
| At times, is emotional stress associated with losing consciousness? | 1 |
| Has anyone ever noted your head turning during a spell? | 1 |
| Has anyone ever noted that you are unresponsive, have unusual posturing or jerking limbs during your spells, or have no memory of your spells afterwards? (Score as yes for any positive response.) | 1 |
| Has anyone ever noted that you are confused after a spell? | 1 |
| Have you ever had spells of lightheadedness? | –2 |
| At times, do you sweat before your spells? | –2 |
| Is prolonged sitting or standing associated with your spells? | –2 |
The patient has seizures if the point score is ≥1 and syncope if the point score is <1.
From Sheldon R, Rose S, Ritchie D, et al: Historical criteria that distinguish syncope from seizures, J Am Coll Cardiol 40:142–148, 2002.
Pseudo-syncope
Functional or psychogenic syncope is often mistaken initially for true syncope.7,9 These patients often have an antecedent history of true vasovagal syncope, which usually becomes more frequent before presentation. The patients are usually young women who faint extremely frequently. Only the rare patient faints several times weekly to several times daily, but this is not unusual in pseudo-syncope. The spells can last many minutes, giving an appearance of syncope lasting up to an hour. The history usually does not include the transient autonomic symptoms that often accompany vasovagal syncope, and patients rarely volunteer a history of visual disturbances that often precede true syncope. These visual changes—blurring, tunneling down, spots, stars, and visual blackening—are caused by retinal hypoperfusion and are a reliable marker of a true hemodynamic disturbance.9 An antecedent history of physical or sexual abuse often exists. The diagnosis can occasionally be confirmed if the patient has a fainting spell in monitored situations such as during a tilt-table test (TTT) or while undergoing electroencephalography (EEG).
Orthostatic Hypotension
Orthostatic hypotension is defined conventionally as a drop in systolic blood pressure of at least 20 mm Hg or a drop in diastolic blood pressure of at least 10 mm Hg. New and more restrictive definitions are under consideration. The drop in blood pressure is a measurement, not a diagnosis. Several syndromes are characterized by presyncope or syncope caused by orthostatic hypotension. Not infrequently, symptomatic orthostatic hypotension occurs because of volume depletion of blood after a heavy meal. Initial orthostatic hypotension occurs within 5 to 20 seconds of arising quickly, often in association with standing and walking. Presyncope is much more common than syncope.9,35 The hypotension is caused by a transient draw-down of central arterial volume to the exercising bed, accompanied by a delay in baroreceptor-mediated compensation. No specific treatment is necessary. Drug-induced orthostatic hypotension is often caused by polypharmacy, including diuretics, vasodilators, and adrenergic receptor antagonists. Syndromes of orthostatic hypotension, in which symptoms develop over longer periods, usually occur in older patients. Here, the primary symptom is presyncope, and the longer the patient is upright, the worse is the lightheadedness. Syncope occurs less commonly and usually after prolonged upright posture. Primary autonomic failure occurs in the setting of one of several relatively uncommon neurodegenerative diseases such as pure autonomic failure, multiple system atrophy, and Parkinson disease. Finally, secondary autonomic failure can occur with damage to the autonomic nervous system caused by systemic diseases such as diabetes, Parkinson disease, or multiple-system atrophy.3,4,9,35
Cardiac Syncope
Syncope caused by arrhythmias or structural heart disease is much less common than vasovagal syncope but carries a risk of significant morbidity and death.4,5 It is usually caused by an abrupt drop in cardiac output and typically occurs within the first few seconds of onset of the arrhythmia. The most likely reason is that baroreceptor-mediated compensatory vasoconstriction takes 10 to 20 seconds to have an effect, leaving the patient unprotected for that time. However, reports also document the association of vasovagal syncope with supraventricular tachycardia (SVT), atrial fibrillation (AF), and inappropriate sinus bradycardia.36–38 Factors such as arterial baroreceptor sensitivity, posture of the patient, volume status, associated cardiopulmonary disease, and reflex peripheral vascular compensation all play a role in determining whether tachycardia could be the reason for the syncope. The diagnosis and management of these arrhythmias are covered in detail in other chapters of this book.
Patients often present with undocumented syncope and a documented substrate that might be related to the cause, such as syncope with bifascicular block.39–43 No clear consensus or firm evidence exists to guide treatment for these patients. In this setting, reasonable equipoise exists, for example, between implanting a loop recorder or performing an invasive electrophysiological study (EPS) and simply performing a therapeutic procedure such as pacemaker insertion. Importantly, the patients should be assessed for other cardiovascular risk factors that may take precedence in investigation and therapy. Patients with severe left ventricular systolic dysfunction and syncope usually require an implantable cardioverter-defibrillator, even though this might not treat neurally mediated syncope.4
Diagnosing the Cause of Syncope
Diagnostic Approach
General principles with good evidence to support them have been reviewed in detail in the recent European Society of Cardiology (ESC) guidelines.4 History and physical examination are fundamental to the diagnosis of syncope. A detailed and accurate history provides a diagnosis in most cases, a prognosis for vasovagal syncope, an understanding of patient needs and preferences, and an economic basis for further investigation. The efficient use of investigations, as appropriate, should be based on the flow charts presented in the ESC document (Figure 48-1).
The first step in the differential diagnosis is to identify whether the TLOC episode was truly syncope, that is, a self-limited loss of consciousness caused by transient global hypoperfusion. Other causes of TLOC, such as epileptic seizures, narcolepsy, cataplexy, true drop attack, and hypoglycemic coma, should be briefly considered; however, in day-to-day clinical practice, they are rarely mistaken for syncope. Important and life-threatening potential causes such as cardiac syncope from arrhythmias or structural heart disease should be carefully considered in every case. Specific investigations can be selected on the basis of the initial assessment.1,4,6
History and Physical Examination
The initial evaluation of history, physical examination, and the electrocardiogram (ECG) often leads to a certain diagnosis. A Dutch study with more than 500 patients with TLOC found that, based on a 2-year follow-up, physicians who used only history, physical examination, and ECG made a diagnosis in 63% of the patients, with a diagnostic accuracy of 88%.44 If the diagnosis is certain, usually no further (or minimal) investigations are needed, and the focus then shifts to management. With an uncertain diagnosis, further careful, directed testing is usually necessary. The rare patient with frequent, recurrent episodes, especially in the context of other somatic concerns, may have a psychiatric illness.
Patients with syncope may describe their episodes in a variety of ways, including “dizziness,” “fainting,” “lightheadedness,” and “blackouts.” A prodrome may last from less than a second to several minutes. Most episodes occur when the patient is in the upright posture, occasionally in the sitting posture, and very rarely in the supine position. Patients often report additional presyncopal episodes and being able to avert syncope by sitting or lying down quickly. Patients are usually unresponsive for less than a minute and often fatigued for hours or even days after an episode but are oriented and responsive within minutes. Pallor is often observed.4–79
Recent work has suggested the importance of quantitative diagnostic scores.45–47 Quantitative histories and diagnostic scores are well known in other fields, and they improve diagnostic accuracy. A comprehensive set of questions that provides a single diagnosis out of all possible diagnoses does not exist; rather, the questions need to be asked in sequences of groups. First, determine if this is syncope or another diagnosis such as epilepsy. A point score that distinguished seizures from syncope with an accuracy of 94% was recently published (see Table 48-1).47 Second, determine whether the patient has structural heart disease by inquiring about his or her cardiovascular history. If the patient does not have structural heart disease, the diagnostic difference between reflex neurally mediated syncope and arrhythmic syncope depends on specific provocative situations, associated symptoms and signs, age of onset, and underlying arrhythmias. A quantitative score (Table 48-2) that works with more than 90% accuracy in patients younger than 60 years is widely available.46 Older patients often require further investigation.48 Another quantitative score has 99% sensitivity and 68% specificity for ventricular tachycardia (VT) in patients with structural heart disease (Table 48-3), and it is accurate with regard to diagnosis as well as arrhythmic and fatal outcomes.45
Table 48-2 Calgary Syncope Symptom Score for Structurally Normal Hearts
| QUESTION | POINTS (IF YES) |
|---|---|
| Is there a history of at least one of the following: bifascicular block, asystole, supraventricular tachycardia, diabetes? | –5 |
| At times, have bystanders noted you to turn blue during your faint? | –4 |
| Did your syncope start at age 35 years or older? | –3 |
| Do you remember anything about being unconscious? | –2 |
| Do you have spells of lightheadedness or faint with prolonged sitting or standing? | 1 |
| Do you sweat or feel warm before a faint? | 2 |
| Do you have spells of lightheadedness or faint with pain or in medical settings? | 3 |
The patient has vasovagal syncope if the point score is ≥–2.
From Sheldon R, Rose S, Connolly S, et al: Diagnostic criteria for vasovagal syncope based on a quantitative history, Eur Heart J 27:344–350, 2006.
Table 48-3 Calgary Syncope Symptom Score for Structural Heart Disease*
| QUESTION | POINTS (IF YES) |
|---|---|
| Was your age at first faint at age 34 years or later? | 3 |
| Are you a male? | 1 |
| Have you become lightheaded or fainted with prolonged sitting or standing? | –1 |
| Have you become lightheaded with stress?† | –2 |
| At times, are you tired for more than 1 minute after a fainting episode? | –2 |
| Do you have recurrent headaches? | –2 |
The patient has ventricular tachycardia if the score is ≥1 and vasovagal syncope if the score is <1.
* Diagnostic questions to determine whether syncope is caused by ventricular tachycardia or vasovagal syncope.
† The term “stress” was used in its colloquial sense and meant to capture psychosocial stress.
From Sheldon R, Hersi A, Ritchie D, et al: Syncope and structural heart disease: Historical criteria for vasovagal syncope and ventricular tachycardia, J Cardiovasc Electrophysiol 21:1358–1364, 2010.
These scores have several uses. They provide validated, quantitative, objective, diagnostic inclusion criteria that, by reducing the need for TTT, provide rapid translation of clinical trial results into community practice. In this setting, they provide reproducible criteria for clinical studies.49 Although these scores should not be the sole basis for diagnosis, they are useful aids in clinical practice. Finally, they may eventually provide a framework for evidence-based definitions of syndromes.
Finally, current understanding about predicting vasovagal syncope recurrence is much clearer.50–54 Almost all the predictive power is in the year immediately before presentation. A patient who has not fainted in the previous year has only a 7% risk of syncope in the next year, but a patient with at least one faint in the previous year has a 42% risk of syncope in the next year.50
Selection of Tests
The first stage of testing screens for a substrate for syncope, including careful clinical assessment, a resting ECG, and, when appropriate, short-term ECG monitoring, echocardiography, and blood work.6 This provides a presumptive diagnosis in most patients as well as a prognosis, which is particularly important because syncope with underlying heart disease is a risk for sudden cardiac death (SCD). The yield of blood tests in detecting the cause of syncope is only 2% to 3%, detecting mostly electrolyte or metabolic abnormalities causing seizure. A hematocrit level less than 0.3 is useful for the detection of gastrointestinal bleeding.27,55,56 Blood tests (hemoglobin, electrolytes, cardiac biomarkers) should be performed only in the presence of a clinical suspicion of occult hemorrhage, arrhythmias/seizures caused by electrolyte or metabolic abnormalities, or myocardial infarction (MI).
Tests such as echocardiography, coronary angiography, and radionuclide scintigraphy are of little value in unselected populations and should only be used when indicated by clinical assessment.57 The primary role of this form of testing is to establish or exclude the presence of potentially contributory structural heart disease. An echocardiogram should be obtained in the presence of known heart disease, data suggestive of structural heart disease, syncope secondary to cardiovascular cause, syncope with exertion, or a murmur.
Computed tomography (CT) of the head is performed in nearly half of all syncope patients but has a less than 1% likelihood of detecting a cause.58 Similarly, conventional EEG is rarely useful in the investigation of unselected patients with syncope. In contrast, although the yield of an ECG is less than 5% in unselected patients, it is noninvasive and inexpensive and can detect life-threatening abnormalities. Accordingly, it is recommended in all patients.
The second stage of testing is aimed at the specific cause of syncope. Here, provocative testing is used to induce a syncopal episode or to detect an abnormal physiological response that might explain the history of syncope. This includes tests such as TTT and EPS. Interpretation of these tests requires considerable judgment because these tests induce a physiological response (not the event itself) and are plagued by lack of sensitivity, lack of specificity, or both. An alternative approach is the use of long-term ECG monitoring with a Holter monitor and external and implantable loop recorders to document the cardiac rhythm associated with a spontaneous episode of syncope. Current devices do not detect hypotension.1,4,6
Tilt-Table Testing
TTT creates orthostatic stress that results in venous pooling and may simulate the hemodynamic changes seen in vasovagal syncope.59–67 The test is performed with continuous ECG and blood pressure monitoring; patients are initially placed in the supine position, and the table is tilted to an angle of 60 to 80 degrees. The patient is kept at this angle for 20 to 45 minutes; further drug provocation with isoproterenol, clomipramine, or nitroglycerin can be used for another 15 to 20 minutes. If symptomatic hypotension and bradycardia occur, the patient is promptly returned to the supine position to prevent injury and the test is concluded. Syncope or presyncope with a cardio-inhibitory response, vasodepressor response, or both reproducing the patient’s symptoms is considered a positive outcome.
As simple as TTT seems, these tests, in fact, contain numerous variables that affect the test outcome.65 Controlled studies have shown that the likelihood of positive tests depends on the angle and duration of the head-up tilt, whether and how a drug challenge is used, the number of head-up iterations during the test, the volume status of the subject, and the subject’s age. A variable correlation exists between the symptoms provoked by TTT and by the subject’s clinical symptoms and widely variable and usually unvalidated hemodynamic criteria to indicate a positive test. The test has not been validated against a gold standard population, and different TTT protocols identify patient populations that do not completely overlap. Patients with otherwise idiopathic syncope have the same baseline symptoms and symptom burden, the same clinical outcome, and the same statistical relationships between baseline symptoms and clinical outcome, regardless of a positive or negative TTT result.52 Finally, an intractable trade-off between diagnostic accuracy and specificity seems to be present. The mechanism observed with syncope at the time of TTT may not correlate with clinical episodes. Hence TTT should be used only in individuals in whom the history, physical examination, and ECG have not established the diagnosis.
Electrocardiographic Monitoring
The implantable loop recorder (ILR) is an ideal device for obtaining rhythms on a continuous basis.4,6,68 Its use is driven by the importance of symptom-rhythm correlation, particularly in settings in which syncope could have one or more causes. For example, AF may cause syncope because of tachycardia onset or pauses after arrhythmia termination. In addition, the high population prevalence of vasovagal syncope often raises vasodepression as a competing diagnosis when arrhythmias are considered.
The ILR is implanted under the skin and does not require any leads or external sensors; it has a pair of sensing electrodes on the shell. It can be automatically activated by an arrhythmia (high and low rate events) or by the patient using an external programmer. Current models have a battery life of 3 years and record the ECG signatures of infrequent syncopal episodes. Several studies have confirmed the usefulness of the ILR in establishing a symptom-rhythm correlation for syncope.68–78 On the whole, syncope recurs in 30% to 50% of patients. A few patients have tachyarrhythmia during syncope, but most of the heart rhythm disturbances are bradycardic. Many of these appear to be caused by reflex-mediated suppression of the sinoatrial and atrioventricular nodal functions during vasovagal syncope. However, the most common rhythm detected is sinus rhythm; presumably the cause of syncope is vasodepression without bradycardia. In the largest study, bradycardia was seen to accompany syncope in less than 30% of cases. The International Study on Syncope of Uncertain Etiology (ISSUE) investigators implanted ILRs in 111 patients with probable vasovagal syncope, regardless of their TTT results. Syncope recurred in 34% of patients, with marked bradycardia or asystole being the most common recorded arrhythmia during syncope (46% and 62%, respectively). The ISSUE investigators reported a classification of rhythm findings that helps distinguish among the causes of bradycardia (Box 48-1).69
Box 48-1 Classification of Rhythm Findings During Syncope as Documented by an Implantable Loop Recorder
