History & Physical Examination
According to several prospective studies, the initial clinical evaluation establishes the cause of syncope or suggests the necessary diagnostic test in up to 85% of the patients in whom a diagnosis will eventually be made. A detailed history and physical examination are therefore essential parts of the initial clinical evaluation. Relevant historical information includes all details leading up to the event, precipitating factors (micturition, cough, exertion), premonitory symptoms (aura), onset (sudden or slow), associated symptoms (palpitations, chest pain, headache), activity (at rest or with exercise), position (standing, sitting, changing position), and details about the episode (injury, incontinence, rapid recovery versus postictal state) and the frequency and severity of the events. The history should include factors suggestive of cardiac or other systemic illnesses, such as a family history of cardiac illness, arrhythmias, syncope, sudden death, or pacemaker implantation. Because about 10% of syncope is caused by the use of medications and recreational drugs, information regarding their use, prescribed dosages, and the amount actually taken is very important. All witnesses to the event (family, friends, bystanders) should be thoroughly interviewed because they can often supply details that the patient cannot. These witnesses may be able to provide information about the patient's complaints just prior to the event and observations during both the event (eg, pulse rate and rhythm, color, presence of spontaneous breathing, seizures, or seizure-like activity) and recovery. Electrocardiographic (ECG) recordings made by paramedics at the scene or recorded en route to the hospital and in the emergency department may provide important clues.
All patients need a complete cardiac, peripheral vascular, and neurologic examination, including an assessment of positional blood pressure and heart rate. Cardiac murmurs may be suggestive of structural heart disease, such as valvular stenosis. Differential blood pressure and pulse intensity may suggest aortic dissection or subclavian steal syndrome. Focal neurologic findings may point to seizure, stroke, or transient ischemic attack. The development of similar symptoms with upright posture and a corresponding decrease in blood pressure implicate orthostatic hypotension.
Several bedside maneuvers can be used to provoke syncope or presyncopal symptoms in appropriate patients. Arm flexion and extension may be used to provoke symptoms of subclavian steal syndrome; neck flexion and extension may elicit the symptoms of vertebrobasilar insufficiency. Open-mouthed hyperventilation for 1–3 minutes may elicit symptoms described in the history. CSM (when not contraindicated by presence of bruits or known carotid arteriosclerotic disease) can be performed at the bedside with ECG and blood pressure monitoring. Although the technique is not standardized, carotid massage is usually performed with the patient in the supine position, with 5 seconds of firm massage of each carotid body. Note that simultaneous bilateral massage is never done. A positive test is defined as at least 3 seconds of asystole with hypotension or reproduction of symptoms. Because of the high false-positive rate for CSM in the elderly, the diagnosis of carotid sinus hypersensitivity should only be considered if clinical events are associated with activities that press or stretch the carotid sinus.
Toxicology screens and medication levels may provide useful information and should be ordered if suggested by the patient's or the witness's history. Figure 16–2 outlines a suggested diagnostic approach.
Diagnostic approach to syncope. CSM, carotid sinus massage; ECG, electrocardiogram; EPS, electrophysiologic study; HUT, head-up tilt-table testing; LV, left ventricular.
Moya A, et al. Task force for the diagnosis and management of syncope, European Society of Cardiology, European Heart Rhythm Association, Heart Failure Association, Heart Rhythm Society, for the diagnosis and management of syncope. Eur Heart J
Noninvasive Diagnostic Studies
A 12-lead ECG should be part of the routine clinical evaluation of syncope. A normal 12-lead ECG generally portends a good prognosis, with a very low incidence of either cardiogenic causes or diagnostic findings during invasive electrophysiologic testing. Unfortunately, the initial ECG rarely establishes arrhythmia as the cause unless complete heart block, ventricular tachycardia, or another abnormality is present at the time of the tracing. Given the unpredictably episodic nature of syncopal spells and the fact that most patients recover completely from them prior to the ECG, it is rare that the 12-lead ECG is diagnostic. More often, certain findings will suggest the possibility of a specific diagnosis. For example, Q waves suggestive of previous myocardial infarction correlate with abnormal electrophysiologic studies and the presence of inducible ventricular arrhythmias. Delta waves suggestive of Wolff-Parkinson-White syndrome make supraventricular tachycardia a very likely diagnosis. A long QT interval suggests torsades de pointes, and bifascicular block correlates with abnormal electrophysiologic findings, including high-degree AV block and inducible ventricular arrhythmias.
The most common abnormalities found in patients with syncope are bifascicular block, prior myocardial infarction, left ventricular hypertrophy, sinus bradycardia, and first-degree or Wenckebach AV block. Although these findings are all nonspecific, they may suggest a cardiac cause. The ECG or rhythm strips recorded by paramedics, the emergency department, or hospital ward lead to a specific diagnosis in about 10% of patients. The most common diagnoses include ventricular tachycardia and bradyarrhythmias caused by sinus node dysfunction or high-degree AV block.
If the history, physical examination, and ECG do not suggest the diagnosis, or if underlying heart disease is suspected, an echocardiogram is a valuable diagnostic tool. Echocardiography may diagnose the likely cause of syncope (aortic stenosis, hypertrophic heart disease); but, more commonly, it is useful in directing further evaluation. Because morbidity and mortality with syncope are directly related to the presence and severity of structural heart disease, the echocardiogram can aid the physician in assessing the patient's prognosis and the necessity for further invasive evaluation. For example, the finding of a low left ventricular ejection fraction suggests ventricular arrhythmias and would be an indication for further electrophysiologic evaluation or an implantable defibrillator. Unsuspected findings on echocardiography are reported in 5–10% of unselected patients with syncope. Although this is similar to the ECG, the cost of the study limits it to persons with no obvious cause or suspected underlying heart disease.
Exercise stress testing may be useful in patients with exertional symptoms. Exertional hypotension may occur as a result of underlying structural heart disease, chronotropic incompetence, or severe conduction disease resulting in AV block with increased atrial rates. Supraventricular and ventricular arrhythmias may be provoked with exercise. Hypotension and bradycardia at the termination of exercise can be diagnostic of reflexive vasomotor instability. Also, exercise or other forms of stress testing in those who cannot exercise may detect myocardial ischemia—a potential substrate for ventricular arrhythmias.
Prolonged ECG monitoring can be useful for documenting transient bradyarrhythmias or tachyarrhythmias. The most common method used is a Holter ambulatory ECG recording. Typically, two surface ECG leads are recorded for a period of 24–48 hours. Holter recording can be particularly helpful in diagnosing bradyarrhythmias, such as significant sinus pauses and transient high-degree AV block. When interpreting Holter recordings, clinicians must recognize that several abnormalities can occur in healthy, asymptomatic patients, and correlation with symptoms is often essential. Premature atrial and ventricular contractions, brief and paroxysmal atrial tachycardia, episodic AV Wenckebach block, sinus bradycardia, sinus pauses of up to 3 seconds especially when asleep, and nonsustained ventricular tachycardia can all be seen in normal, asymptomatic patients. Sinus pauses of longer than 3 seconds, Mobitz II AV block, complete heart block, and frequent nonsustained ventricular tachycardia are far less prevalent.
Because the correlation of symptoms with an arrhythmia in patients with syncope provides the most valuable information, it is essential for the patient to keep an accurate diary of symptoms and activity during the recorded interval. Ambulatory monitoring is often useful in excluding arrhythmia mechanisms of syncope when patients experience syncope or presyncope without associated arrhythmias. Conversely, ambulatory monitoring may reveal significant conduction abnormalities or arrhythmias when the patient is asymptomatic. Frequent sinus pause of ≥ 3 seconds with associated atrial fibrillation indicates significant sinoatrial dysfunction. Asymptomatic Mobitz II AV block suggests distal conduction disease, with the possibility of prolonged AV block resulting in Adams-Stokes attacks. Nonsustained ventricular tachycardia in patients with significant left ventricular dysfunction (ejection fraction < 40%) correlates with a risk of sudden death from sustained ventricular arrhythmias and warrants further electrophysiologic evaluation (see section on Invasive Electrophysiology Studies).
A significant limitation of Holter ambulatory ECG recording is how infrequently patients experience either syncope or associated symptoms during the test. The results of studies suggest that Holter monitoring captures the heart rhythm during spontaneous syncope in only 4–10% of patients. For this reason, external ambulatory loop recorders have been used extensively for the evaluation of syncope. These devices record a single ECG lead continuously and can be worn by a patient for weeks. When activated by the patient or an observer, a rhythm strip is saved that includes several minutes surrounding the syncopal or presyncopal episode (Figure 16–3). The rhythm strip is sent to the laboratory using trans-telephonic equipment for added convenience for the patient and physician. Loop recorders are useful for evaluating patients with episodic syncope, presyncope, or dizziness, with or without associated palpitations.
Event recorder monitor strip received from a patient with a prior history of syncope, recurrent presyncope, and structural heart disease. The patient underwent an electrophysiology study and was found to have inducible monomorphic ventricular tachycardia that was treated with an implantable cardioverter-defibrillator.
For patients with infrequent symptoms, small loop recorders can be implanted under the skin and have a battery life of 1 year. They can be activated by the patient or a companion remotely, but newer models automatically record abnormal rhythms. This feature is especially valuable for patients who are rapidly incapacitated by their symptoms and cannot reliably activate a device. Although implantable loop recorders were once reserved as a last-resort diagnostic strategy, some physicians recommend earlier implantation because studies have shown diagnostic yields up to 87%.
Head-Up Tilt-Table Testing
Gravitational shifts in blood volume have long been recognized as a stimulus to neurocardiogenic syncope (also known as vasomotor, vasovagal, neurally mediated, or neurocardiogenic syncope). The use of the tilt table as a provocative maneuver in the diagnosis of unexplained syncope is decreasing because of concerns about the sensitivity, diagnostic yield, and reproducibility of the test. In patients with a normal cardiac evaluation, the pretest probability of neurocardiogenic syncope is high, so tilt-table testing is unlikely to be of value. The technique starts with monitoring the fasting patient for 10 minutes in the horizontal position, using noninvasive brachial or finger blood pressure, oxygen saturation, continuous ECG, and if somatization disorder is suspected, electroencephalogram (EEG) (true syncope can be differentiated from malingering). The patient is then tilted 60–80 degrees for up to 45 minutes; in children and adolescents, positive tests tend to occur sooner, and a period of 30 minutes is sufficient. The tilt produces a shift in blood volume distribution away from the central circulation and thorax to dependent peripheral vessels. This causes a decrease in central venous pressure, ventricular filling, stroke volume, and mean arterial blood pressure. Normally, activation of the baroreceptor-vasomotor reflex (described earlier) and renin-angiotensin system and release of catecholamines result in maintenance of blood pressure through increased heart rate and vasoconstriction. Monitoring of a normal passive tilt would show a small decrease in systolic blood pressure, with an increase in diastolic blood pressure, mean arterial pressure, and heart rate. All of these are considered normal adjustments to gravitational stress.
The test is considered positive if syncope or presyncope occurs with hypotension, with or without bradycardia. The patient is then quickly placed in the horizontal position, where normal compensatory mechanisms restore blood pressure and consciousness. The test is considered negative if symptoms and hemodynamic abnormalities fail to occur by 45 minutes of tilt. The tilt can be repeated with a provocative agent, such as the β-agonist isoproterenol, in selected patients (discussed later).
As previously discussed, various degrees of hypotension and bradycardia secondary to a paradoxical reflex that increases vagal tone and decreases sympathetic tone develop in susceptible patients. Both hypotension and bradycardia are present (a mixed response) in most patients. Hypotension usually predominates, however, and tends to occur before bradycardia (as shown in Figure 16–1). Hypotension that occurs alone, without bradycardia, is considered a purely vasodepressor response. Rarely, a patient may have a purely cardioinhibitory response (asystole).
The test has been shown to be 80–90% reproducible and specific, with a low false-positive rate (< 10%) in asymptomatic individuals. However, sensitivity ranges from 25% to 80% depending on the population studied. The 2006 American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) scientific statement of the evaluation of syncope no longer recommends routine tilt-table testing for undiagnosed syncope. However, there are some patients in whom the diagnosis is unknown after a cardiac evaluation and the history is not helpful. Some of these patients would benefit from a tilt-table test, whereas in others a presumptive diagnosis of neurocardiogenic syncope is adequate.
Routine laboratory tests (blood counts and chemistries) rarely reveal useful diagnostic information. Unless specifically suggested by the history and physical examination, it is not recommended in the evaluation of syncope. Likewise, EEG, computed tomography, or magnetic resonance imaging studies are of little use in patients whose history is not suggestive of a neurologic cause. These tests should be considered only in those patients whose neurologic history and physical examination are suggestive of seizure or other neurologic condition. Although routinely performed, the usefulness of transcranial Doppler ultrasonography in patients with syncope is unclear. Transient ischemic attacks rarely result in syncope without other associated symptoms. In patients with bruits on physical examination, ultrasonography is reasonable and may be useful in leading to a diagnosis.
Invasive Electrophysiology Studies
An invasive electrophysiology study (EPS) uses multielectrode catheters inserted percutaneously and guided under fluoroscopy or by magnetic sensors to specific cardiac locations. Electrode recording and pacing protocols are then performed to assess the patient's conduction system, including sinoatrial and AV nodal function and the distal conduction system (His-Purkinje). In addition, supraventricular and ventricular arrhythmias may be induced and their mechanisms determined in susceptible patients. In selected patients, ablation of the arrhythmic substrate with radiofrequency energy can be performed, often curing the patient of the condition.
Because patients are generally supine and sedated during EPS, one significant limitation is the inability to definitely correlate induction of arrhythmias with syncope; however, a rapid tachycardia associated with a significant decrease in systolic blood pressure generally supports the clinical importance of inducible arrhythmias. Induction of certain arrhythmias, such as atrial fibrillation, atrial flutter, polymorphic ventricular tachycardia, and ventricular fibrillation, can be a nonspecific finding. Asymptomatic patients with normal hearts can have all these induced with aggressive stimulation protocols.
The AHA/ACCF scientific statement on the evaluation of syncope does not recommend routine EPS in patients without underlying heart disease. It does recommend EPS in patients with cardiac disease and syncope that remains unexplained after appropriate evaluation, especially if the ejection fraction is reduced. In addition, EPS is reasonable in patients with recurrent unexplained syncope without structural heart disease and a negative head-up tilt test. In patients with no structural heart disease, normal ECG, normal ambulatory monitoring, and recurrent syncope not associated with injury, EPS is usually not diagnostic. EPS is not indicated in patients with a known cause of syncope for whom treatment will not be guided by electrophysiology testing.
The most significant finding at EPS is the induction of ventricular tachyarrhythmias. In addition, the induction of supraventricular tachycardias with associated hypotension is considered a positive study. Other significant findings include a prolonged corrected sinus node recovery time longer than 1000 ms, prolongation of the His-to-ventricle activation interval greater than 100 ms (normally 35–55 ms), or induction of infra-Hisian conduction block during rapid atrial pacing. These three findings are associated with significant bradyarrhythmias. Unfortunately, the diagnostic sensitivity of EPS for bradyarrhythmias is low, and further ambulatory monitoring is often necessary after a nondiagnostic EPS.
Krediet CT, et al. The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive? Europace.
Romme JJ, et al. Diagnosing vasovagal syncope based on quantitative history taking: validation of the Calgary Syncope Score. Eur Heart J
Strickberger SA, et al; American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke; Quality of Care and Outcomes Research Interdisciplinary Working Group; American College of Cardiology Foundation; Heart Rhythm Society; American Autonomic Society. AHA/ACCF Scientific Statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation: in collaboration with the Heart Rhythm Society: endorsed by the American Autonomic Society. Circulation