A Practical Approach to Syncope: Clinical Evaluation

Syncope, the transient loss of consciousness and postural tone with spontaneous recovery, is one of the most frequent and frustrating symptom complexes with which patients and physicians alike have to cope. Its myriad causes can render diagnosis enormously expensive. Listed here are the steps needed for a full clinical evaluation to diagnosing syncope. Bedside Evaluation For an effective beside evaluation, one has to keep in mind certain important concepts: * Uncertainty in diagnosis is almost unavoidable. The challenge to the diagnostician is to narrow the margin of doubt. Since today’s syncope can become tomorrow’s sudden cardiac death (SCD), it behooves the clinician to carefully evaluate its causes. * Prognostically, two distinct groups of syncope can be identified. Syncope due to cardiovascular causes carries approximately a 25% one-year mortality rate, while noncardiac syncope portends no excess mortality.1 Middlekauff et al2 and later Kapoor et al3 surmised that the excess mortality may be more related to the underlying heart disease rather than to additional risks incurred because of the syncope itself. However, these data may not be relevant nowadays, as both heart failure and ICD therapy have dramatically evolved since those reports. * An astute history is extremely important for evaluating syncope. It is, in fact, the basis upon which the subsequent diagnostic investigation rests. * Syncope is due to transient global cerebral hypoperfusion. The causes to consider fall into four major categories: obstructive cardiopulmonary disorders, arrhythmias, blood pressure regulation disorders, and situational syncope (Table 1). * Syncope is rarely, if ever, a manifestation of primary neurological disorders. Large studies in the past three decades have dispelled the notion that isolated syncope can be a manifestation of transient ischemic attacks.4 History First, one needs to substantiate that the problem is indeed syncope and not epilepsy, hysteria, conversion, or any other condition. Several seconds of nonspecific lightheadedness and dizziness coupled with a gradual loss of vision or motor tone or both are often characteristic presyncopal symptoms. Specific sensory and/or motor symptoms suggest, however, that the problem may be a seizure. Syncope, when viewed in its broadest definition of global hypoperfusion, can present with isolated transient loss of motor tone and hardly any impaired consciousness, especially in the elderly. Examination of the events after the syncopal spell is also important. A patient who recovers quickly and without any lasting after-effects is likely suffering from a primary arrhythmic cause of syncope. Alternatively, patients with neurocardiogenic syncope will display one or more manifestations of vascular collapse and/or vagal overstimulation, such as nausea, vomiting, sweating, shivering, or the urge to defecate or urinate. Most characteristically, there is almost always a variable period of lassitude that can be extended for hours or even days. The presence of such symptoms following the event does, by no means, rule out arrhythmias as a cause of syncope. However, absence of these symptoms essentially rules our neurocardiogenic syncope as a primary cause. When the presence of syncope is confirmed, the history alone will positively identify the cause of the most characteristic “situational” syncope syndromes, such as emotional syncope, cough syncope, micturition syncope, and carotid sinus syncope. For these patients, minimal or no testing is required (carotid sinus massage). In all other instances, the history will be used to gather corroborating clues that will help further narrow the differential diagnosis. In this context, the following should be evaluated: * Number and frequency of events. Patients with frequent episodes are unlikely to have a malignant arrhythmia as a cause, especially if the recurrences are distributed over months or years. * Presence of organic heart disease. A patient with left ventricular dysfunction is at an increased risk, but other patients with no left ventricular dysfunction can also have a malignant cause of syncope (e.g., right ventricular dysplasia or long QT syndrome). * Family history. This is especially important in the young and apparently healthy patient, for whom the initial reflex of the physician may be to dismiss the events as having a benign vasovagal cause. However, a family history of Wolff-Parkinson-White syndrome, familial cardiomyopathy, long QT syndrome, right ventricular dysplasia, hypertrophic cardiomyopathy, and especially SCD at a young age should be treated with extreme concern. * Medications. Vasoactive medications can obviously cause orthostatic hypotension, but antiarrhythmic and psychotropic drugs, diuretics, and even antihistaminic and antifungal agents can lead to serious ventricular (generally polymorphic) arrhythmias related to QT prolongation or electrolyte disturbances or both. * Age. Younger patients (Physical Examination During the physical exam, one should be aware of the following: * Vital signs. A resting bradycardia, or an irregular pulse, can indicate sick sinus syndrome. * Orthostatic hypotension. When orthostatic hypotension is abrupt and associated with reflex tachycardia, volume depletion should be suspected. When it is gradual and unaccompanied by increasing heart rate, autonomic dysfunction is the likely diagnosis. * Skin turgor and complexion. Pallor can indicate anemia. When it is associated with decreased skin elasticity, it may indicate hypovolemia due to acute blood loss. * Cardiovascular examination. The cardiovascular exam will demonstrate or reveal “obstructive” lesions associated with syncope. It may also indicate the presence of left ventricular dysfunction. In a patient with known hypertension, a funduscopic examination should be performed to detect papilledema and/or retinal hemorrhages. These may be telltale signs of a transient hypertensive crisis causing syncope. (The pathophysiology here would be extreme intracranial vasoconstriction causing a “no flow” situation.) * Carotid sinus massage. This is an easy and cost-effective way to indirectly assess sinus node function. The results, however, should be interpreted with caution. Many older, asymptomatic patients display long and technically abnormal pauses (> 3 seconds). A long pause is helpful only if associated with a highly suggestive history of syncope related to maneuvers that exert spontaneous pressure on the carotid sinuses (e.g., tight collars, shaving). Further Work-Up: Diagnostic Tests for Syncope Once the history and physical examination are properly obtained, diagnostic testing can then be individualized. A shotgun approach can and should be avoided — it is costly, unyielding, and disturbing to the patient. Generally, most patients, except for those with highest risk of cardiac death, will not require hospitalization for the work-up of undiagnosed syncope. Many tools can assist the diagnosis of syncope. Guided by information retrieved from the bedside evaluation and careful consideration of the capabilities and limitations of the variety of observational and provocative tests available for laboratory evaluation, the diagnostician can outline an efficient, high-yielding work-up that usually can be conducted in the outpatient setting with minimal risk and at a relatively low cost. Tests that can be helpful and cost-effective include electrocardiograms (ECG), echocardiograms, signal-averaged electrocardiogram (SAECG), 24-hour and event monitoring (temporary or implantable), tilt testing, and electrophysiologic studies (EPS). Observational Tests * Electrocardiogram. Although the ECG may reveal diagnostic abnormalities in only 5% to 10% of cases, it can provide clues in another 20% to 30% (e.g., old Q waves, various degrees of AV and bundle branch block, pre-excitation, left ventricular hypertrophy [LVH], nonsustained ventricular tachycardia [VT]). The presence of left bundle branch block (LBBB) is noteworthy in that patients with syncope, old MI, and bundle branch block BBB have a 68% rate of VT induction (65% for RBBB, 74% for LBBB).5 * Echocardiogram. An echocardiogram is of little help when there is no cardiac history and the physical examination and ECG are normal. Its chief usefulness is in providing an evaluation of left ventricular function in patients with suspected heart disease or uncovering otherwise silent valvular calcifications in patients with conduction system disease. * Signal-Averaged ECG. In a patient with syncope and known CAD, an abnormal SAECG should mandate EP testing for the induction of VT. Patients with suspected ARVD and syncope will nearly always display late potentials on their SAECG. * Holter monitoring. Holter exams are rarely diagnostic because Event recorders. These devices allow ECG events to be captured and recorded for later transtelephonic transmission. Hand-held recorders are essentially useless for patients with syncope. More useful are endless loop recorders, which can be attached to the patients for weeks. These allow taped retrieval of events up to several minutes after onset and, therefore, record a “clinical” event as it is occurring. Implantable recorders are pacemaker-sized units that are surgically inserted in a subcutaneous prepectoral pocket. A single-lead ECG is monitored and 15-minute snapshots can be later retrieved via a communicating unit. The battery-operated device has an expected two-year life. Long-term monitoring presents a potentially serious drawback in that patients must be exposed to the risks of at least one more syncopal event to be diagnosed. A more surreptitious pitfall is that monitor-obtained bradycardiac manifestations of vasovagal syncope cannot be analyzed in the context of antecedent blood pressure changes and may, therefore, lead to unnecessary pacemaker implants. Provocative Tests Head Up Tilt Testing While autonomic dysfunction can be identified easily at the bedside, to be elicited, neurocardiogenic syncope generally requires the use of more stringent tilt testing with or without isoproterenol, nitroglycerin and/or edrophonium stimulation. In a study of 156 patients with syncope of unknown origin, we induced syncope by simple, unstimulated tilt testing in 63 patients. Another 35 patients displayed abnormal but nonsyncopal responses for a total yield of 63%. Of the abnormal tests, 85% were related to neurocardiogenic (i.e., vasodepressor, vasovagal) syncope, while most others were due to mild autonomic dysfunction.6 Regarding sensitivity and specificity of tilt testing, the following is useful: * Tilt testing can effectively uncover neurocardiogenic syncope.6 * Day-to-day variability in response and induction of neurocardiogenic syncope is common, unavoidable, and simply reflects expected variability of autonomic nervous system physiology. * The sequence of blood pressure and heart rate changes before induced syncope can help outline specific preventive therapy.6 * A test can be abnormal and “diagnostic” if syncope is not induced. * The clinical events surrounding the syncopal spell are important for interpreting tilt test results. Tilt testing is indeed most yielding in young healthy adults, yet the stakes are high if a malignant arrhythmia is missed. For instance, in the setting of sudden, exercise-induced loss of motor tone accompanied by fleeting loss of consciousness and followed by instant recovery, an abnormal tilt test is highly suspect as being false-positive. Observations made during tilt testing suggest the following6: 1. During vasovagal and/or vasodepressor syncope, hypotension is always present and appears to be triggered by sudden neural autonomic imbalance rather than by bradycardia. When bradycardia occurs, the hypotension worsens and the process becomes self perpetuating. The presence of antecedent hypotension explains the relative inefficacy of pacing as a treatment for neurocardiogenic syncope. 2. A clinical state of sympathetic overactivity often precedes vasovagal or vasodepressor syncopal attacks. 3. Vasovagal and/or vasodepressor syncope are often associated with abnormalities in blood volume and its distribution. These observations allow us to construct the following pathophysiologic scheme: As hypovolemia or venous incompetence accentuate the degree of diminution of venous return during head up tilt, left ventricular filling is diminished and sympathetic stimulation results in tachycardia and increased inotropy. In other words, a situation is a set up whereby the ventricle is strongly contracting around an empty cavity. This causes inappropriate stimulation of the afferent C-fibers in the left ventricle, thus releasing an efferent parasympathetic inhibitory discharge.7 With hyperbeta adrenergic syndrome (a form of POTS), a similar pathogenesis may apply even though venous pooling may not be exaggerated. In this case, reduction in left ventricular filling occurs secondary to the marked tachycardia and its attendant decrease in diastolic filling time. Similarly, observations made during vasovagal syncope that is precipitated by phobic stimuli reveal that a state of sympathetic overactivity almost always precedes the syncopal attack. Drug-stimulated tilt tests will increase the overall sensitivity (but decrease the specificity) of tilt testing especially when their application is tailored to the clinical situation (e.g., isoproterenol for the patient with suspected hyperadrenergic, nitroglycerin stimulation for the patient with suspected excessive venous pooling, edrophonium for the patients with suspected hypervagotonia). Total blood and plasma volume measurements (radioisotopic serum dilution dilation) will identify patients with absolute hypovolemia (essential hypovolemia) as the underlying trigger to vasodepressor syncope (VDS).8 In contrast, tilt testing with high Ace bandage wrapping would help identify with a “dynamic” hypovolemia (i.e., due to excessive venous pooling). In these patients, an abnormal baseline tilt test would normalize port Ace wrapping. Exercise Testing Exercise testing has a relatively low-yield in the work-up of syncope. Isolated syncope is rarely a result of ischemia. Similarly, coronary angiography is not indicated for the work-up of isolated undiagnosed syncope and should be performed only when other symptoms or factors dictate its use. Exercise testing may be helpful to induce VT in patients with dilated cardiomyopathy, long QT syndrome and RV outflow tract VT. Electrophysiologic Testing EP studies use pacing techniques to initiate arrhythmias by atrial and/or ventricular stimulation. Although somewhat invasive, EP testing is very safe, carrying a morbidity potential roughly a tenth of that of diagnostic angiography. It is routinely performed on an outpatient basis. Regarding advantages and pitfalls of EP studies, consider the following: * EP studies are most effective for inducing sustained monomorphic VT. The results are disease-specific. The highest sensitivity and specificity occur in patients with old MI and no acute ischemia, in patients with left ventricular ejection fraction (LVEF) Summary Multiple tools are available to aid the work-up of undiagnosed syncope. When applied judiciously, tilt testing, long-term event monitoring and electrophysiologic studies emerge as the most informative techniques available. Neurologic tests and coronary angiography are rarely useful and are not indicated as part of the evaluation of isolated syncope.