Fredrick J. Jaeger
This chapter focuses on core material related to the evaluation of patients who present with syncope of unknown origin. It reviews the indications and contraindications for various salient procedures and diagnostic maneuvers to evaluate patients who present with syncope. Highlighted among these are head-up tilt table testing to provoke and confirm neurocardiogenic syncope and electro-physiologic testing to assess for atrioventricular (AV) node and sinoatrial (SA) node dysfunction and inducibility of supraventricular tachycardia (SVT) and ventricular tachycardia (VT), which could be responsible for recurrent syncope. It is critical, in this era of evidence-based medicine and quality outcomes, health maintenance organizations (HMOs), diagnosis-related groups (DRGs), and limitations of diagnostic testing availability, that a concise, logical, streamlined approach to the evaluation of patients with syncope be employed. Several useful algorithms can be found in the literature (Fig. 32.1).1 Recently, it was proposed that emergency departments adopt a streamlined approach to syncope patients that will allow more efficient utilization of resources, identifying high-risk patients and avoiding unnecessary admissions for low-risk patients.2
FIGURE 32.1 Example of diagnostic algorithm for patients with LOC. TLOC, transient loss of consciousness; ECG, electrocardiogram; EEG, electroencephalogram; MRI, magnetic resonance imaging; MI, myocardial infarction; PE, pulmonary embolism; CSM, carotid sinus massage; EP studies, electrophysiologic studies; VQ scan, ventilation perfusion scan; CT, computed tomography; ILR, insertable loop recorder. (Reprinted from Kaufmann H, Wieling W. Syncope: a clinically guided diagnostic algorithm. Clin Auton Res. 2004(Suppl 1);14:i87–i90, with permission.)
Syncope, defined as the transient loss of consciousness (LOC) with complete reversibility without subsequent focal neurologic deficit, is a frequent clinical conundrum for cardiologists, internists, and electrophysiologists.3,4 The approach to the syncopal patient is comprised of several algorithms, the aggressiveness of which depends on the seriousness of the syncopal spells, and the presence or absence of structural heart disease. Although the most common etiology of all syncope from all causes and in all groups is probably benign vasovagal syncope, a syncopal event in a patient with significant coronary disease, prior myocardial infarction (MI), severe left ventricular (LV) dysfunction, congestive heart failure, or in the context of known complex ventricular arrhythmias may be malignant and a harbinger of subsequent sudden cardiac death.
EPIDEMIOLOGY OF SYNCOPE
In the early 1980s, it was recognized that syncope is a common reason for emergency room visits and admissions.5 Many of these patients were suspected to have either reflex or neurocardiogenic/vasovagal syncope, but testing was limited. Simultaneously, techniques of electrophysiologic testing were being developed, ambulatory monitoring was in its infancy, and tilt table tests were still a research tool. Then, as today, the workup for patients with unexplained syncope was extremely expensive. Even with recent constraints, DRGs, and so on, the evaluation of patients with syncope still has been estimated to be $1 billion annually. Although syncope for the most part was probably suspected to be due to underlying neurocardiogenic syncope, in the 1980s, there was no good test or “gold standard” to determine which patients were susceptible or truly vasovagal. When the tilt table was introduced and recognized as a valuable electrophysiologic modality, it entered intense and extensive utilization. The late 1980s and early 1990s represent the probable zenith of its use. Between 1992 and 1994, tilt table procedures escalated from approximately 6,000 to 14,000 per year. Recent years have seen a downtrend in the number of tilt table tests being performed, particularly as our clinical acumen has become better at identifying patients who are experiencing vasovagal syncope. Patients with syncope and a normal heart virtually always have underlying vasovagal syncope, even despite a negative tilt table test. Given the constraints of limited reproducibility, specificity, and sensitivity, tilt table tests, although still frequently performed, are reserved for those patients who meet specific criteria of recurrent syncope, for which no ready explanation can be provided. Although tilt table numbers have declined for suspected vasovagal syncope, the last few years have seen a burgeoning of requests to investigate for underlying dysautonomias such as postural orthostatic tachycardia syndrome (POTS).
In general, determination of the underlying etiology for syncope is almost always largely presumptive. Rarely do spontaneous clinical events occur during cardiac or telemetric monitoring. The goal in the evaluation of syncope is therefore not only to determine a likely underlying diagnosis with a relative degree of certainty and alacrity but also to ensure that no life-threatening entities are responsible. Diagnostic studies such as head up tilt table tests and electrophysiologic studies (EPS) are merely tools to examine various components of the autonomic nervous system and the cardiac electrical system, and the results must be interpreted with cautious skepticism. Although it is reassuring to convince oneself of a relatively benign type of syncope, as in vasovagal, it is axiomatic that the patient should always be assumed to have more malignant underlying causes of syncope until proven otherwise. Merely assuming that a positive tilt table test explains syncope in a patient with an ejection fraction (EF) of 25% from known coronary artery disease is clearly clinically inappropriate and fraught with danger. To further confound the differential diagnosis, many patients have syncope that is multifactorial. For example, an elderly patient with tendency toward sinus node dysfunction and carotid sinus hypersensitivity may also be on medications that result in hypovolemia and an inclination toward orthostatic hypotension (OH). All can lead to syncope.
Syncope results from the many potential causes of cerebral hypoperfusion, and textbooks and review articles frequently display long, comprehensive lists of possible etiologies of syncope (Table 32.1).6 In general, these lists can be synthesized and concentrated into five potential causes: (a) reflex syncope, of which vasovagal is the index hallmark and most common cause; (b) OH; (c) arrhythmic syncope; (d) mechanical structural disease such as coronary artery obstructive and valvular cardiac disease; and (e) cerebro-vascular causes. Using this framework and a precise definition of syncope differentiates it from other causes of LOC, including transient ischemic attacks (TIAs) and strokes, hypoglycemia and other metabolic causes, seizure disorders, psychogenic syncope, or vertebral basilar insufficiency (drop attacks). Traditionally, etiologies of syncope have also been even more broadly divided into cardiac and noncardiac causes. This simple paradigm has been utilized to predict clinical outcomes and prognosis. Cardiac causes of syncope may lead to increased mortality compared to noncardiac causes, in which the prognosis is normal and survival is assured.7 However, there is certainly considerable overlap between the cardiac and noncardiac causes. For example, it is now understood that aortic stenosis can cause syncope not only from heart block, or fixed cardiac output, but through reflex mechanisms similar to the Bezold–Jarisch reflex.8
TABLE
32.1 Causes of Syncope
From Brignole M, Lavagna I, Paolo A, et al. Guidelines on management (diagnosis and treatment) of syncope—update 2004. Europace. 2004;6:467–537, by permission of Oxford University Press.
It is often difficult to differentiate an episode of true syncope from other causes of LOC. These include seizure disorders or epilepsy, metabolic abnormalities, cerebral vascular accidents (CVAs) or TIAs, and factitious syncope/pseudoseizures or conversion reactions. The prototypical tonic–clonic movements of epilepsy are well known. Aura, urinary incontinence, and tongue biting are also frequently reported during seizures. Prior head trauma and concussion also may suggest seizures as the cause of LOC. Syncope is frequently accompanied by a few involuntary movements of the head and extremities, which can mimic a seizure disorder. This has been termed “convulsive syncope” and “anoxic seizures” and results from loss of oxygen to the central nervous system (CNS) and brainstem motor centers, and does not reflect an epileptiform phenomenon. These jerking movements are also frequently observed during ventricular fibrillation induced during electrophysiologic testing or during tilt-induced profound vasovagal episodes. Witnesses to clinical episodes of syncope also frequently report similar movements and ascribe them to seizures. Even trained medical personnel may be quick to assume, incorrectly, that seizures are occurring in these situations.
HISTORY
When a patient presents with syncope of unknown origin, the single most important piece of information is the history. Specific detailed questioning regarding the presence or absence of structural heart disease, valvular heart disease, coronary artery disease, previous MIs, prior syncope,9 family history, and so on can quickly delineate the high-risk patient from those at low risk. Historical factors related to a syncopal event can also help point in a specific direction. Situational syncope during phlebotomy, during prolonged standing, in a dentist’s office, in a restaurant, in church, following alcohol ingestion, and so on is almost universally vasovagal or neurocardiogenic. The presence of prodromal symptoms, such as nausea or diaphoresis, usually also heralds the onset of the vasovagal reflex. Frequently, the patient with vasovagal syncope may have postsyncopal symptoms that can last from hours to a day or so, including weakness, nausea, fatigue, and a tendency to recurrent syncope.
In contrast, a lack of prodrome or presence of previous MI or heart failure certainly points to a more malignant etiology of syncope, usually mandating hospital admission. Complete and immediate recovery after a syncopal event suggests an arrhythmic etiology, such as VT, SVT, or AV block. Injuries are uncommon with vasovagal syncope, as the patient usually tends to crumble to the ground, rather than fall abruptly. In contrast, severe injuries and automobile accidents are suggestive of a more serious arrhythmic etiology such as extreme tachycardia or bradycardia.
Calkins et al.10 have retrospectively evaluated the value of the history and the differentiation of patients with recurring syncope. Eighty patients with recurrent syncope undergoing a complete evaluation were provided comprehensive questionnaires focusing on the features of their syncopal spells. Patients underwent extensive electrophysiologic testing, tilt table testing, and ambulatory recording when appropriate, with the diagnosis confirmed in these 80 patients. The origin of syncope was broadly broken down into two varieties: relatively benign syncope due to vasovagal or neurocardiogenic etiology versus a more serious type of syncope due to underlying AV block or VT. As expected, symptoms prior to the onset of syncope, such as blurred vision, palpitations, nausea, and generalized warmth or diaphoresis, were more consistent with neurocardiogenic syncope. Similar symptoms after the syncopal event were also more consistent with neurocardiogenic syncope. In contrast, little or no warning prior to the syncopal event was more consistent with AV block or VT. Patients with AV block or VT tended to be older and of male gender, owing to the predominance of atherosclerotic disease. In addition, patients with more dangerous syncope etiologies generally reported no prior episodes, specifically having less than two episodes of syncope in their lifetime. These features, together with a history, can help determine whether a patient requires admission for further investigation.
CLINICAL FEATURES OF SYNCOPE
Often, witnesses to the syncopal event can provide other clues as to the possible cause, particularly regarding the duration of syncope. Prolonged episodes of unresponsiveness, such as 7 to 10 minutes or more, are unlikely to be due to vasovagal or arrhythmic etiologies and instead suggest neurologic processes. Sudden LOC followed by fairly quick resumption of consciousness suggests tachyarrhythmias, such as VT, SVT, or atrial fibrillation with a post conversion pause. Patients who experience vasovagal syncope frequently have several minutes of prodromal symptoms, followed by LOC. The episode of unconsciousness with vasovagal syncope varies but may last 3 to 4 minutes, particularly if the patient cannot be rendered supine. A patient with vasovagal syncope may arouse slowly, with considerable confusion and postsyncopal vagal symptoms.
PHYSICAL EXAMINATION
The physical examination of patients with syncope is generally directed toward cardiac auscultation for the presence of valvular disease, carotid bruits, assessment of pulses, irregular pulse and heart rhythm. For patients with vasovagal syncope, the physical exam and the cardiovascular exam will generally be entirely normal. However, the presence of murmurs, S3 or S4 gallops, and displaced point of maximal intensity (PMI) may point to the presence of LV dysfunction. Similarly, bigeminal rhythms and trigeminy may also suggest the presence of LV dysfunction in a patient with syncope. Findings of congestive heart failure, jugular venous distention, hepatojugular reflux, hepatosplenomegaly, and bibasilar pulmonary rales also point to the presence of LV dysfunction in a patient with syncope. The finding of atrial fibrillation on physical examination or during electrocardiography (ECG) is very important and suggests tachybrady syndrome or sick sinus syndrome. Gross neurologic evaluation showing evidence of lateralization or focal neurologic deficits is also important, suggesting either cardioembolic phenomena from atrial fibrillation or carotid atherosclerotic disease, both of which can cause episodic LOC.
Carotid sinus massage can be performed safely at the bedside, but is contraindicated in the presence of carotid bruits, known carotid stenosis, TIAs, and CVAs. During ECG monitoring, sequential bilateral gentle carotid massage can be performed for 5 to 10 seconds, with the patient in a supine, slightly elevated head position. Positive responses consist of cardioinhibitory pauses >3 seconds. Patients with true carotid sinus syndrome frequently show an instantaneous and abrupt response with a prolonged cardioinhibitory response to massage with LOC.
Careful observations of postural responses of blood pressure and heart rate are often useful when evaluating patients with syncope. The presence of marked OH in patients with syncope is highly suggestive. OH is defined as a systolic blood pressure decline of >20 to 30 mm Hg or a diastolic blood pressure decline of >10 mm Hg. These can either be elicited immediately on assuming an upright posture from supine baseline or occur more gradually at 1 to 3 minutes. OH is very common, particularly in the elderly, and may be multifactorial, often resulting from medications (diuretics, vasodilators, etc.) and intrinsic dysfunction of autonomic reflexes that can occur with aging, strokes, diabetes, alcohol use, and atherosclerosis of cardiopulmonary, aortic arch, and carotid sinus baroreceptors. Marked abrupt or instantaneous OH is particularly prominent in multisystem atrophy (MSA, previously called Shy–Dragger syndrome) or in pure or primary autonomic failure (PAF, previously called Bradbury–Eggleston syndrome). Patients with MSA may exhibit features of Parkinson disease (PD), but PD itself is an important etiology for OH as well, either from intrinsic autonomic failure or from antiparkinson medications.11 Patients with PD often experience unexplained falls, which may result from OH, gait disturbances, or “on—off” phenomena.
DIAGNOSTIC TESTING FOR SYNCOPE
Laboratory investigation for syncope of undetermined etiology begins with an ECG to identify arrhythmias or previous MIs. The presence of Q waves indicative of previous MI, long QT interval, left bundle branch block, ventricular pre-excitation, or left anterior hemiblock are all significant and may suggest the need for further invasive investigation. Syncope in a patient with trifascicular block (Fig. 32.2) is a Class IIA indication for implantation of a permanent pacemaker.12,13 Signal-averaged ECG, although once touted as a major advancement in diagnostic capability for syncope, is now reserved largely for the detection of late potentials, predominantly in patients with transient ventricular ectopy, which may signify underlying arrhythmogenic right ventricular cardiomyopathy (ARVC). Unfortunately, most of these patients have an intrinsic QRS abnormality consistent with a right bundle branch block, which makes the signal-averaged ECG less specific.
FIGURE 32.2 Complete right bundle branch block, left anterior hemiblock, and first-degree AV block, the so-called trifascicular block. This finding in patients with syncope suggests intermittent high-degree AV block and may indicate a need for a permanent pacemaker.
Stress Testing and Echocardiography
When clinically indicated, particularly with physical findings or an ECG suggesting the presence of structural heart disease, initial testing often includes functional studies to assess for an ischemic etiology. Echocardiography is useful to assess for mechanical or structural lesions, such as hypertrophic cardiomyopathy, aortic stenosis, occult LV systolic dysfunction, or in the case of ARVC or RV dysfunction. Routine incorporation of these modalities is costly and unnecessary in the vast majority of syncope cases, particularly when the clinical history, ECG, and physical examination are normal and suggest a benign cause.
Ambulatory Electrocardiographic Monitoring
Ambulatory electrocardiographic monitoring as a baseline may be helpful, particularly for those patients with recurrent syncopal episodes, and may disclose paroxysmal atrial fibrillation, SVT, or nonsustained VT. Routine Holter monitoring in the absence of structural heart disease is frequently unrewarding. Systems utilizing event-recording technology, such as the King of Hearts (Instromedix) and others may be more helpful to disclose intermittent episodes of bradyor tachyarrhythmias. Newer wireless and bluetooth devices (e.g., Lifewatch—Instromedix, Cardionet) can provide full disclosure with continuous EKG monitoring to a central monitoring station for immediate reporting, and are collectively termed mobile cardiac outpatient telemetry (MCOT). (Fig. 32.3). These devices, however, are quite costly and are not indicated for high-risk cohorts.
FIGURE 32.3 Cardionet ambulatory arrhythmia monitor.
Ambulatory blood pressure monitor devices are also available and are frequently utilized for patients suspected of having intermittent orthostasis. However, these devices can be quite clumsy and burdensome, and often do not react quickly enough to record substantive data. Future ambulatory and implantable ECG event recorders currently in development may also allow simultaneous blood pressure recording.
Implantable Loop Recorders
The implantable loop recorder (ILR) (Fig. 32.4) (Medtronic— Reveal, St Jude Medical—Confirm) was designed specifically for patients with infrequent syncopal episodes in which Holter monitoring or 30-day event recordings fail to demonstrate the etiology of their syncope. The ideal patient is one who has recurrent syncope, palpitations, or suspected SVT once or twice a year, escaping conventional monitoring.
FIGURE 32.4 Reveal (Medtronic) ILR.
Current indications are for patients with syncope of undetermined etiology with a structurally normal heart. It should not be implanted in high-risk patients with syncope and severe LV dysfunction. It has also been used in patients with fleeting or suspected SVTs for whom electrophysiologic testing is contemplated. An emerging indication is for patients who have drug-refractory seizures in whom an arrhythmic etiology from either tachy- or bradycardia is suspected.
Several studies have utilized the ILR in their diagnostic algorithms to determine the cause of syncope. The Randomized Assessment of Syncope Trial (RAST) evaluated 60 patients randomized through either the conventional diagnostic paradigm of electrophysiologic testing, tilt table test, and extensive recording or accelerated loop recorder implants.14–16 Follow-up was for 1 year. Patients with loop recorder implants had an earlier time to diagnosis. The International Study of Syncope of Undetermined Etiology (ISSUE) investigators examined the use of the loop recorder implant in several important patient subgroups, including those with: (a) syncope and a normal heart that had a negative tilt table test; (b) syncope and a bundle branch block and a negative EPS; and (c) syncope with cardiomyopathy and a negative EPS. The first cohorts of the ISSUE study consisted of 82 patients with syncope and a negative tilt and 29 patients with syncope and a positive tilt.17 Both groups received ILRs. During follow-up, there was an approximate 34% syncope recurrence rate in both groups despite treatment. Interrogation of the ILRs showed that the underlying electrocardiographic abnormalities during syncope were consistent with a vasovagal etiology in the vast majority of patients. This suggested that in patients with a normal heart, syncope is still most likely due to underlying vasovagal phenomena, despite a negative tilt test. With this observation, as well as others on tilt test limitations, it has become apparent that the tilt table test may be superfluous in the evaluation of patients with syncope and a normal heart. The ISSUE study further went on to implant loop recorders in patients who had bundle branch block, syncope, and a negative electrophysiologic test, including a challenge with Ajmaline.18 During follow-up, syncope recurred in >40% of patients, and the most common finding was AV block or asystole, although sinus arrest was also observed. Therefore, this supported the current practice of implanting pacemakers in patients with syncope, normal LV function, and bundle branch block, which is currently a Class IIA indication. Finally, the ISSUE investigators implanted loop recorders in patients with ischemic and dilated cardiomyopathies and syncope following a negative EPS.19 These patients usually now receive a defibrillator. A total of 35 patients were implanted with loop recorders following a negative EPS. During a relatively short follow-up of 6 ± 5 months, there was a 17% recurrence of syncope, predominately due to bradyarrhythmias. No VT was observed, although the follow-up was short. Therefore, it still would be prudent to consider implanting a defibrillator in patients with severe LV dysfunction and syncope.
Recently, the ILR was utilized to disclose a new, previously poorly defined entity of prolonged paroxysmal high-degree or complete AV block in patients with recurrent syncope, otherwise normal hearts, normal EKGs without evidence of significant conduction abnormality, and no evidence that these episodes were due to a vagal etiology.20 These patients were observed to have varying degrees of transient high-degree AV block causing near syncope and were then treated with permanent pacemakers which eliminated their episodes. The actual prevalence of this disorder is unknown, but it certainly highlights the value of early utilization of ILRs in diagnostic paradigms.
No further investigations are probably required in a patient with historical absence of structural heart disease who has a normal ECG and a single episode of syncope that is typically vasovagal. However, if there are risk factors for coronary artery disease, such as a male aged >50 years, additional testing frequently includes assessment of LV function with an echocardiogram as well as an exercise test. In the absence of structural heart disease, for a single episode of syncope without malignant features, no other testing is typically required. However, if any of the above significant indicators of structural heart disease are present, then further investigation such as Holter monitoring and possibly EPS are warranted. The finding of nonsustained VT in the presence of LV dysfunction, and an EF <40%, especially in the setting of syncope, is indicative of the need for electrophysiologic testing and defibrillator implantation.
Electrophysiologic Testing
For patients who present with syncope of undetermined etiology, electrophysiologic testing has been described as the “gold standard” for demonstration of supraventricular and ventricular arrhythmias, AV nodal or His–Purkinje disease, and bradyarrhythmias, all of which can be responsible for syncope. Indications for electrophysiologic testing in patients with syncope are given in Table 32.2.21 This procedure, introduced clinically in the late 1970s, involves the insertion of several intravascular catheters to record intracardiac atrial electrograms, His potentials, and ventricular electrograms. Atrial and ventricular programmed electrical stimulation may induce sustained monomorphic VT or SVT. Measurement of AV node refractoriness and Wenckebach cycle length may demonstrate significant AV nodal disease that could be responsible for intermittent Mobitz type I, II, or high-degree AV block, particularly in elderly patients. Similarly, a prolonged His–ventricular (HV) interval suggests that syncope may be due to heart block. His–Purkinje conduction can be challenged by administration of IV procainamide with subsequent marked HV prolongation.22 In general, electrophysiologic testing is less helpful in the evaluation of the sinus node (Table 32.3). Occasionally, sinus node recovery times (SNRTs) can demonstrate prolonged pauses indicative of sinus node dysfunction. Attempted induction of sustained monomorphic ventricular tachycardia (SMVT) consists of programmed electrical stimulation of the right ventricle at two sites (RV apex and RV outflow tract), usually with sequential repetitive drive trains of 400 to 600 milliseconds followed by one, two, or three ventricular extrastimuli. Other protocols attempt to induce SMVT by using more rapid repetitive bursts (300 to 350 milliseconds) in the ventricle. The finding of SMVT is significant and suggests the need for an implantable cardioverter-defibrillator (ICD).
TABLE
32.2 Clinical Features Suggesting Need for Electrophysiologic Testing of Patients with Syncope
TABLE
32.3 Electrophysiology Study—Components
Almost every tachyarrhythmia is amenable to some form of radiofrequency catheter ablation. AV nodal reentry, AV reentry via accessory pathways, and atrial tachycardias are frequently mapped and ablated in a straightforward fashion. In previous decades, EPS was performed much more frequently for syncope evaluation than it is at present. Current clinical practice reserves EPS for a few select cases, such as patients with LV dysfunction, suspected SVTs, conduction abnormalities, and those who may be candidates for radiofrequency ablation. Rarely is EPS performed for syncope in patients with normal hearts and normal ECGs, given the likelihood of a vasovagal cause in this patient subset. Patients who present with syncope in the presence of LV dysfunction, a previous MI, or an EF < 35% to 40% qualify for empiric ICDs given the MADIT 2 and SCD-Heft data.23 There are still several clinical situations in which EPS is performed to evaluate syncope patients (see Table 32.2). American College of Cardiology/American Heart Association (ACC/AHA) guidelines are listed in Table 32.4.
TABLE
32.4 Guidelines for EPS for Patients with Syncope
From Zipes DP, DiMarco JP, Gillette PC, et al. Guidelines for clinical intracardiac electrophysiological and catheter ablation procedures: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Intracardiac Electrophysiologic and Catheter Ablation Procedures), developed in collaboration with the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol. 1995;26: 555–573, with permission from Elsevier.
SPECIFIC ETIOLOGIES OF SYNCOPE
Neurally Mediated Syncope
Vasovagal syncope (also called neurocardiogenic syncope, empty heart syndrome, and ventricular syncope) is the most common of the neurally mediated syncopes. All of these syndromes result from disturbances or perturbations of the autonomic nervous system. A partial list of some of the more commonly observed neurally mediated syncopes is given in Table 32.5. Syncope arising from aortic stenosis or hypertrophic obstructive cardiomyopathy is felt to have a significant neurally mediated component and may precipitate the stimulation of C fibers in the posterior left ventricle in a fashion similar to vasovagal syncope (Bezold–Jarisch reflex).8 In addition, it is suspected that in patients with syncope due to recurrent atrial fibrillation, SVT, or VT, there may also be a neurally mediated component in which atrial vasodepressor reflexes result in significant vasodepression, causing a drop in blood pressure and contributing to the LOC independent of a low cardiac output.
TABLE
32.5 Neurally Mediated Syncope
Symptoms preceding the vasovagal response are typical and can serve as clues to the nature of the syncopal spell. Vagal symptoms such as diaphoresis, nausea, vomiting, and diarrhea are common both before and after the syncopal spell. The patient may be observed to be very pale, and may complain of either being cold or excessively warm. Frequently, patients report presyncopal loss of vision, which may persist for a variable amount of time. This has been described as “graying out.” Tinnitus or loss of hearing is frequently described as occurring prior to the syncopal event. Patients can be observed, both spontaneously and during head-up tilt table tests, to be hyperventilating and may complain of shortness of breath, representing an autonomic trigger reflex. The onset of yawning during a head-up tilt table test can often herald the onset of a vasovagal event. Sinus tachycardia associated with the episode may be perceived as palpitations and be confused with SVT, or may mimic a chest discomfort complaint.
During unconsciousness, patients may be observed to experience generalized myoclonic jerking, the so-called anoxic seizure or convulsive syncope. This may mimic the features of epilepsy to both medical and nonmedical bystanders, and may complicate the differential diagnosis. When patients awaken, there may be a slight confusion, which can also mimic a postictal state. If patients try to ambulate too quickly, they may experience another episode of syncope.
The most common precipitant of vasovagal syncope is from so-called noxious stimuli, such as flight or fight, pain, venipuncture, fear, or anxiety. Other situations in which marked venous pooling or sequestration of blood volume in lower extremities or splanchnics takes place may also precipitate the vasovagal response. These include prolonged rigid standing, as in soldiers at attention; pregnancy, in which the gravid uterus prevents venous return from the inferior vena cava (IVC) compression; or from inadequate venous return, such as in hypovolemia, diuretic treatment, anemia, or acute hemorrhage. Prolonged bed rest, as in patients recovering from illness, can also lead to a propensity for vasovagal syncope. It has been known for several decades that astronauts returning from even brief exposure to microgravity are also predisposed to a vasovagal-type syndrome. The “first-dose phenomenon,” such as occurs with certain vasodilators and nitrates, has also been shown to precipitate a vasovagal-type response, as does beta-blocker withdrawal.3
The clinical scenario of typical vasovagal syncope begins with abrupt vasodepression, followed by a marked cardioinhibitory response. Similar to cardioinhibitory responses observed during carotid sinus hypersensitivity testing, cardioinhibitory responses can also occur during head-up tilt table testing. These include sinus pauses of 3.5 seconds or more, as well as junctional rhythm, marked sinus bradycardia, or also commonly AV block of the first-, second-, or even third-degree variety. Less commonly, vasodepressor syncope occurs in which an isolated drop in blood pressure accompanies the syndrome. Even during pure vasodepressor syncope and hypotension, the heart rate can be observed to be inappropriate for the degree of hypotension. Cardioinhibitory responses that accompany vasovagal syncope have also been called “extrinsic sick sinus syndrome” and are myriad. We have frequently observed prolonged episodes of asystole, incidentally recorded by monitoring. Asystolic events occurring during vasovagal syncope can also be observed during phlebotomy-provoked fainting. Reflex asystolic pauses are occasionally mistaken for intrinsic SA or AV node disease and may promulgate erroneous consideration and referral for a permanent pacemaker. However, reflex-mediated asystolic pauses are benign, with a favorable prognosis, and pacemaker implantation is not usually necessary.24 Other types of brady-arrhythmia can be observed both clinically during vasovagal syncope and during tilt table testing, including junctional bradycardia, marked sinus bradycardia, and first-, second-, or third-degree AV block. A unique form of atrial fibrillation can be initiated by or cause a vasovagal response. This form of atrial fibrillation is felt to be vagal in origin, resulting from marked parasympathetically mediated heterogeneity of atrial refractoriness, leading to precipitation of atrial fibrillation. The heightened or augmented parasympathetic autonomic status can then trigger concomitant vasovagal fainting.3
The natural history of recurrent vasovagal syncope is heterogenous, but some clinical observations merit specific mention. Vasovagal episodes tend to cluster. It is not uncommon for patients to have relative quiescence of their episodes of syncope, only to have episodes reemerge with increasing frequency, particularly around times of major life stressors. Patients with previously recurrent vasovagal syncope may have no further episodes following an initial positive tilt table test. In this respect, demonstration of the underlying etiology provides reassurance to the patient of the relatively benign nature of the syncope and may have a therapeutic affect. The occurrence of frequent spontaneous resolution of vasovagal syncope, even in untreated patients, can make the evaluation of the efficacy of subsequent pharmacologic interventions spurious. Similarly, up to 75% of patients may have a negative tilt table test on subsequent tests performed months or years later, which makes obtaining reproducibility difficult. Natale et al.25observed 54 patients with neurocardiogenic syncope who declined treatment. During follow-up, nearly 70% of the patients had no further episodes.
The pathophysiology of vasovagal syncope historically has been attributed to the activation of C fibers in the posterior and inferior wall of the left ventricle during a vigorous contraction of a relatively empty ventricle (Bezold–Jarisch reflex).8 This initiates a reflex-mediated sympathetic withdrawal, leaving the heightened parasympathetic activation relatively unopposed. Withdrawal of sympathetic activation causes peripheral arterial and arteriolar vasodilation and hypotension, and the parasympathetic predominance causes bradycardia (Fig. 32.5).26 This concept has been challenged by the observation of a vasovagal-type response in cardiac transplant patients, who presumably would not have intact afferent and efferent innervations capable of propagating the vasovagal reflex.27 Alternative theories for vasovagal pathogenesis have been proposed, including various neurohumoral and neuroendocrine peptides, epinephrine, and the ubiquitous nitric oxide.28 There also appears to be a genetic predisposition to vasovagal susceptibility. Patients with fainting episodes frequently report that their parents or siblings also were fainters. As yet, no specific gene markers have been identified. A recent intriguing but highly conjectural proposal to explain genetic origins of the vasovagal response was that during the times of humans as hunter–gatherer–warriors, the tendency to faint, especially during battles, may have afforded a survival benefit by feigning death and avoiding mortal wounds. This has been called the “Paleolithic threat hypothesis.”29
FIGURE 32.5 Example of prolonged asystole and cardioinhibitory response during a vasovagal syncope provoked by tilt table testing.
Vasovagal syncope can be divided into two categories: a relatively benign form in which patients have a recognized precipitating stimulus and a more malignant variety in which there is no recognized stimulus, but the patient may have prolonged asystole and severe injuries, with loss of driving privileges and employment.30 This latter variety is frequently found to have some underlying autonomic abnormalities or blood volume distribution abnormalities, such as hypovolemia or marked venous pooling. In many cases, no abnormalities can be found. Future advances in the understanding and treatment of vasovagal syncope will require a better delineation of the pathophysiology.
Head-Up Tilt Testing for Vasovagal Syncope
The head-up tilt table test was initially devised in the mid-1980s as a research tool for the evaluation of postural reflexes. Subsequently, it was recognized as an important clinical tool to induce and provoke vasovagal syncope in susceptible individuals, thereby establishing a diagnosis. In the 1980s and early 1990s, extensive and divergent tilt table protocols were proposed for vasovagal syncope provocation, including protocols with 90-degree tilt for up to 90 minutes and those using tilt tables with saddle support. Some of these protocols were extremely effective at inducing the vasovagal response but possessed spurious specificity. Recently, several consensus panels have convened to standardize the nomenclature and head-up tilt protocol, which currently consists of at least 30 minutes of 70-degree tilt. Higher degrees of tilt (80 to 90 degrees) or more prolonged tilting durations may decrease specificity. Following an initial drug-free tilt test, intravenous administration of the β-agonist isoproterenol can increase the yield but may sacrifice specificity.31,32 An ACC expert panel document regarding tilt table testing for assessing syncope has established indications,31 including recurrent syncope that is thought to be vasovagal but has not been clearly demonstrated to be so. In general, the tilt table test is not utilized in patients with structural heart disease until other causes of syncope have been excluded. Tilt table testing may also be appropriate for patients with a single syncope spell, if they are felt to be high risk—that is, the syncope resulted in, for example, injury or an automobile accident, or for a patient with a high-risk occupation. Furthermore, tilt table testing may be helpful for patients who are demonstrated to have intermittent episodes of AV block, sinus bradycardia asystole, and in whom the intrinsic form of sick sinus syndrome could be present. Tilt table testing is probably not indicated for a patient with structural heart disease, a patient with a single episode of syncope with typical classic clinical features, or in whom other causes of syncope have been demonstrated. There are several specific indications for tilt table testing, including the differentiation of convulsive syncope or anoxic seizures from true epilepsy; in evaluating a patient with unexplained falls, faints, or injuries; to assess the impact of autonomic dysfunction or neuropathies; or to determine the presence of OH. Although it has been speculated that tilt table testing may be helpful in assessing efficacy of therapy, it is not highly predictive.
In addition to these indications, our center frequently utilizes tilt table testing to assess for the presence of overt or covert OH and to gauge response to therapy. Frequently, the orthostatic response is relatively latent and can only be observed after a prolonged period of upright posture. These nonvasovagal drops in blood pressure are often caused by medication, venous pooling, or autonomic insufficiency.
Proposed tilt table testing protocols include adjunctive pharmacologic challenges with edrophonium, adenosine,33 clomipramine, or sublingual nitroglycerin (The Italian Protocol)6,34 to accelerate onset of vasovagal syncope.
Vasovagal Syncope—Pharmacologic Therapy
The initial treatment for vasovagal syncope consists of reassurance, recognition, and avoidance of precipitating factors, expansion of salt and fluid intake, and avoidance of sympathomimetics (cold remedies, caffeine, and tobacco), dehydration, and alcohol. Patients can be instructed to recognize the premonitory symptoms of vasovagal faint plus a few techniques to avoid syncope, such as immediately assuming a supine position with elevated and moving legs to increase venous return. During their prodromal phase, fainters are frequently incorrectly admonished by onlookers to “put their head between their legs” or “go outside to get some fresh air.” Such actions universally result in syncope and are to be discouraged. Although it has not been rigorously tested, repetitive coughing has been observed to abort the faint, and recently a variety of leg crossing and arm movements have also been proposed.35 When episodes are recurrent and recalcitrant to these simple maneuvers, pharmacologic treatment is often required. Initial empiric therapy usually consists of beta-blockers, serotonin reuptake inhibitors, α‐agonists (Midodrine, ProAmatine),36 anticholinergics, or volume expanders such as Florinef (Table 32.6).37,38 Despite extensive observational reports on the efficacy of many medications for the prevention of vasovagal syncope, there are few randomized studies challenging their use.34 Emerging treatment modalities include tilt table training, in which the patient is taught a technique to perform several times daily that simulates the effects of tilt table testing. This approach has shown significant promise in initial reports and is thought to work by allowing postural reflexes to accommodate to the recurrent postural changes, thereby decreasing venous pooling and attenuating and down regulating certain cardiopulmonary baroreceptors, thus increasing the individual’s resistance to vasovagal syncope.39 As mentioned, this simple exercise may be more effective than medications for vasovagal prophylaxis, but its use is limited by the substantial time commitment and required compliance.
TABLE
32.6 Vasovagal Syncope: Pharmacologic Therapy
Beta-Blockers for Vasovagal Syncope
Beta-blockers have long been the mainstay of initial pharmacologic therapy for patients with recurrent vasovagal syncope. Only recently has beta-blockade been subjected to the rigors of clinical trials. In fact, several trials have not shown any significant improvement in the nature of syncope or frequency of syncope in patients treated with beta-blockers compared to placebo.35 Nevertheless, beta-blockers are frequently prescribed, particularly when the patient has sinus tachycardia or POTS preceding the vasovagal response as observed on a tilt table test. The mechanism of action is linked to the drugs’ negative inotropic and chronotropic properties, which decrease LV contraction, avoid mechanoreceptor C-fiber activation, and inhibit the precipitation of Bezold–Jarisch reflex. They may also help to partially offset reflex-mediated vasodepression by leaving ambient α-receptor–mediated vasoconstriction unopposed. It has also been suggested that beta-blockers may have a CNS effect, working by central serotonin-blocking activity. There has been increased concern about the utilization of beta-blockers in that they may transform relatively benign vasovagal episodes into more malignant occurrences by suppressing intrinsic escape cardiac pacemaker activity and inhibiting automaticity.
Treatment of Vasovagal Syncope
Based on the results of a few additional diagnostic tests performed at our facility, we are also able to further guide pharmacologic therapy. We frequently perform blood volume determination using a radioiodine technique, thereby assessing the autonomic reflexes and the degree of venous pooling. If patients are found to have significant hypovolemia from the blood volume determination, then therapy starts with a high-salt diet and Florinef. If the hemodynamic reflexes reveal a hyperkinetic circulation, as seen in POTS, then beta-blockade is the preferred initial therapy. If there is failure of vasoconstriction during upright posture, then vasoconstricting α-agonist medications (midodrine) are initial therapy. Marked venous pooling is frequently found, especially in sedentary patients, and support stocking therapy as well as physical exercise and reconditioning of leg muscles are prescribed. Finally, young patients are frequently “hypervagal,” and power spectrum analysis can show a predominance of the vagal component, suggesting some benefit with anticholinergic therapy. Often, severe cases have been found to have multiple abnormalities and to require multiple drug therapy.
Pacemakers for Vasovagal Syncope
For patients with recurrent episodes of syncope that are refractory to pharmacologic therapy, for those who have high-risk occupations, or for those who experience prolonged asystole on head-up tilt table tests, the implantation of a permanent pacemaker with rate-drop algorithms has been a long-time but controversial option.40 Evidence for the efficacy of pacing for vasovagal syncope came from large retrospective studies in small, nonrandomized cohorts. In the early to mid-1990s, several studies were proposed to examine this potential therapeutic modality. It was recognized that although cardioinhibitory components of the vasovagal response were frequently observed, they occurred later in the response, only after very profound hypotension had occurred. Therefore, pacing only when the heart rate was low was superfluous and probably already too late to abort or prevent the faint. Several proposed pacemaker designs were evaluated in the hopes that earlier detection would help ameliorate the fainting process. One was designed to tachypace at high rates (>90 to 100 beats/min) when it detected a rapidly falling heart rate. It was hoped that rapid pacing would bolster or preserve cardiac output and maintain consciousness. The multicenter VPS trial randomized patients with vasovagal syncope to a permanent pacemaker with rate-drop technology or to conventional (i.e., pharmacologic) therapy.(41) The results demonstrated a dramatic reduction in syncopal recurrences in the pacemaker group. For a brief time after the publication of this trial, pacemakers became a more prevalent component of vasovagal syncope therapy. However, the VPS2 trial, in which patients were randomized to backup pacing only versus pacemakers with rate drop actively programmed, failed to show any benefit from the rate-drop capability and again relegated pacemaker implantation for vasovagal syncope to a relatively last resort in highly selected patients.3,41,42
An alternative to pacemakers with rate-drop algorithms for patients with neurocardiogenic syncope is available in pacemakers from Biotronik. This pacing modality termed “closed loop stimulation” (CLS) uses local intracardiac impedance measurements which mirror the dP/dt, and in theory can detect augmented inotrope and cardiac contractility which could herald an impending vasovagal event, then allowing for a period of rapid pacing. The INVASY trial (inotrope controlled pacing in vasovagal syncope) implanted pacemakers with CLS in 50 patients with recurrent neurocardiogenic and vasovagal syncope.43Patients who received pacemaker CLS showed a tremendous reduction in their syncopal events. Certainly this presents promising alternatives for some patients with recalcitrant vasovagal syncope but clearly further studies need to be performed.
Therefore, given the high rate of spontaneous resolution in the long term, patients can be reassured as to the general eventual favorable prognosis with vasovagal syncope. Pharmacologic therapy is therefore provided as a temporary or short-term solution. Despite the considerable efforts of aggressive pharmacologic therapy and pacemakers, up to 20% to 30% of patients continue to experience recurrent syncope due to vasovagal phenomena.
Postural Orthostatic Tachycardia Syndrome
POTS is an emerging but poorly understood syndrome. Patients present with the perception of exaggerated heart rate responses to tilt and exercise, with palpitations, light-headedness, and syncope.44 This syndrome is different from the inappropriate sinus tachycardia syndrome,14 which may result from intrinsic sinus node hypersensitivity or ectopic atrial tachyarrhythmias. In addition to heart rate responses, patients may have multisystem complaints, including chronic fatigue-type syndrome,45 fibromyalgia, cognitive dysfunctions (Brain Fog), sleep disorders, gastrointestinal and genitourinary abnormalities suggesting a form, albeit mild, of autonomic dysfunction, the so-called partial dysautonomia. This syndrome may overlap such historical syndromes as mitral valve prolapse syndrome, the hyper-β-adrenergic circulatory state, hyperkinetic heart syndrome, soldier’s heart, DeCosta syndrome, and neurocirculatory asthenia. They do have a vasovagal susceptibility, particularly on tilt table testing, although syncope frequently occurs during extreme sinus tachycardia without demonstrable cardioinhibitory responses. Therefore these patients appear to experience a more unusual form of vasodepressor syncope, particularly on a tilt table test. Several distinct varieties of POTS due to various underlying etiologies exist, and there are probably heterogeneous cases due to multiple causes, such as mild autonomic dysfunction, hypovolemia, excessive venous pooling, catecholamine hypersensitivity, norepinephrine transporter deficiency, and many other causes.(11) Treatment can be very difficult and challenging, relying on volume expanders and beta-blockers or calcium channel blockers, selective serotonin reuptake inhibitors (SSRIs), and a host of relatively investigational and off-label medications.11
Whatever the mechanism is for patients with POTS or orthostatic intolerance, concomitant exercise intolerance and subsequent deconditioning certainly leads to exacerbation of symptoms. Recently it was reported that aggressive reconditioning and physical therapy for patients with postural orthostatic tachycardia can lead to significant symptom amelioration and improvement. Exercises that avoid the aggravation from gravity were utilized in an aggressive protocol consisting of a rowing machine, aquatherapy, water walking, etc. in patients with orthostatic tachycardia. In a relatively short-time such as several months, many patients showed dramatic improvement, where previously aggressive pharmacologic and nonpharmacologic approaches had not been helpful. An additional interesting finding in this study was that POTS patients had significantly decreased LV mass, which may explain their borderline hemodynamics, and a tendency for sinus tachycardia. This observation of a smaller heart was termed “The Grinch syndrome” by these investigators.46 Based on this groundbreaking observation, all patients experiencing dysautonomia should pursue aggressive attempts at physical therapy, cardiac rehabilitation, and reconditioning. Certainly, all patients with POTS should augment fluids and salt with at least 5 to 7 g sodium daily, 1 or 2 L of electrolyte-type sports drinks, compression stockings, and elevation of the head of the bed 4 to 6 inches which can help expand blood volume, and improve orthostasis.
Carotid Sinus Syndrome
Although it is not as common as recurrent vasovagal syncope, carotid sinus syndrome accounts for a significant proportion of syncopal events, particularly in elderly patients. Carotid sinus syndrome results when an overactive or hypersensitive carotid reflex precipitates sudden bradycardia, pauses, or asystole, frequently with a vasodepressor reflex. Episodes may be precipitated by maneuvers that activate the carotid sinus reflex. Often gentle or mild pressure can elicit this exquisitely sensitive reflex. Activities such as tying a necktie, a tight collar, head turning, and forced exhalation as in playing an instrument may precipitate the reflex. Carotid sinus hypersensitivity is common, considering the definition of a 3-second or longer pause with carotid sinus massage. This reflex is particularly common in patients with coronary artery disease and may reflect the extent of coronary atherosclerosis. Carotid sinus syndrome is defined by clinically recurring episodes of syncope confirmed secondary to carotid sinus hypersensitivity. It has been suggested that alterations in the carotid baroreceptors are responsible for the syndrome and reflex. Recent work has focused on alterations in the mechanoreceptors and proprioceptive receptors in the surrounding denervated sternocleidomastoid muscles.47 Treatment for the majority of cases of carotid sinus syndrome, particularly when accompanied by the typical cardioinhibitory responses, is comprised of a DDD permanent pacemaker. The accompanying vasodepressor reflex frequently requires the addition of a high-salt diet and volume expander plus the elimination of potential offending medications such as diuretics.
Neurally Mediated Syncope Syndromes
Less common examples of neurally mediated syncope involve various situations with diverse autonomic nervous system inputs. Tussive or cough syncope can be seen in chronic obstructive pulmonary disease (COPD) patients and may occur during violent paroxysms of coughing. This may result from decreased cardiac output from markedly increased intrathoracic pressure or a Valsalva-type precipitation of bradycardia or heart block. There may also be marked turbulence of cerebral vascular blood flow and intracranial pressure during these severe cough episodes. Deglutition syncope, glossopharyngeal neuralgia,48 micturition, and defecation syncope are also reflex syncope episodes that presumably initiate a bradycardic and vasodepressor response. Pacemaker syndrome, which was more frequently observed during the previous decades of VVI pacing, results from atrial vasodepressor reflexes precipitated during retrograde conduction from ventricular pacing with subsequent atrial activation on a closed AV valve, causing canon A waves. These vigorous atrial systoles cause transient hypotension, which may result in syncope. As mentioned previously, aortic stenosis and hypertrophic cardiomyopathy may cause syncope through a fixed cardiac output but may also precipitate the Bezold–Jarisch reflex in a manner similar to a vasovagal cause. Pallid breath-holding spells are unique episodes of syncope, which occur in very young children following a minor injury or startle, after which they hold their breath, becoming pale and faint.49,50 This is probably an infant or pediatric form of vasovagal syncope.
Orthostatic Hypotension in the Elderly
The elderly can be particularly susceptible to marked fluctuations in systemic blood pressure. They are frequently sedentary, leading to attenuation of their postural reflexes. They may demonstrate supine systolic hypertension and hypotension when upright. Patients may frequently experience marked drops in blood pressure, particularly postprandially, with blood volume sequestration in the splanchnics and abdomen.
Arrhythmias as a Cause of Syncope
Virtually any tachy-or bradyarrhythmia can cause symptomatic light-headedness, hypotension, and syncope. This is particularly true in the setting of significant LV dysfunction. Sustained monomorphic or polymorphic ventricular tachycardia in the presence of severe LV dysfunction is an ominous cause of syncope and can quickly progress to lethal ventricular fibrillation. VT in a normal heart is an unusual cause of syncope, although it is now understood that syncope can result from normal heart VT as well as SVT via the recruitment of vasodepressor-type reflexes akin to vasovagal responses. Sick sinus syndrome, paroxysmal atrial fibrillation with significant postconversion pauses, as well as Mobitz type II and complete heart block are also important causes of syncope. Electrophysiologic testing (see section on electrophysiologic testing) and ambulatory monitors are important tools to obtain symptom–syncope correlation. Based on the results of the Madit II, SCD Heft, and Definite trials, patients with depressed LV function from any cause, that is, EF < 35%, should receive ICDs for primary prevention. A patient presenting with syncope who meets these criteria should be presumed to have had VT as the cause and should receive an ICD in an expedited fashion.
Long QT Syndrome
The long QT syndrome (LQTS) is a genetically transmitted disorder of cardiac ion channels, which results in intermittent or persistent prolongation of the QT interval, predisposing to a specific type of ventricular tachyarrhythmia called torsades de pointes (Fig. 32.6).51 Many distinct subtypes have been described and can be associated with congenital deafness (Jervell–Lange–Nielsen) or with normal hearing (Romano–Ward). Ventricular tachyarrhythmias may be precipitated by bradycardia or catecholamine surges. These ventricular arrhythmias may provoke a syncopal event, and can be associated with sudden cardiac death. Family members of confirmed cases should be carefully evaluated for this disorder. Treatment may consist of beta-blockade, pacemakers, or ICDs. Careful examination of the ECG is paramount in all patients, particularly in young patients with a family history of syncope. Normal QT intervals have been described for males and females. Many drugs have been described that prolong the QT interval and may unmask covert patients.6
FIGURE 32.6 LQTS and polymorphic VT in a young patient presenting with syncope.
Syncope and Dilated Cardiomyopathy
Much attention has been focused on the specific clinical scenario of syncope in a patient with a dilated, nonischemic cardiomyopathy. Syncope in patients with dilated cardiomyopathy (DCM) has long been understood to be a poor prognostic sign and portends high mortality, perhaps 50% at 1 year. Electrophysiology testing has poor sensitivity in this group for the provocation of SMVT. Several studies have proposed empiric defibrillators for these patients, and it is now a Class II indication. The recent adoption of SCD-Heft and Definite study guidelines for the implantation of ICDs in DCM patients with an EF < 35% has rendered previous arguments for empiric ICDs moot.
Brugada Syndrome and Arrhythmogenic Right Ventricular Cardiomyopathy
Brugada syndrome is a recently described arrhythmic disorder in which patients are susceptible to ventricular fibrillation and sudden death.52 Patients may present as survivors of sudden cardiac death but may also have symptoms related to transient VT such as palpitations and syncope. Their hearts are structurally normal. The ECG characteristically demonstrates ST-segment elevation and right bundle branch block in the precordial leads (Fig. 32.7). This disorder is most likely due to a genetic abnormality of cardiac ion channels (channelopathy). Brugada syndrome is endemic in Asia, where it is a recognized cause of sudden death and has been observed to occur in families. Sudden death occurs frequently at night, during sleep. Patients with suspicious but nondiagnostic ECGs can be further evaluated in the electrophysiologic laboratory with sodium channel blockade medications such as intravenous procainamide or ajmaline, which may precipitate the characteristic ECG pattern. Flecainide, usually prescribed for atrial arrhythmia, has also been observed to provoke this ECG pattern in otherwise unsuspected patients. Patients diagnosed with Brugada syndrome should receive a defibrillator if they are symptomatic or if there is a family history of sudden cardiac death.
FIGURE 32.7 ECG findings of right bundle branch block and precordial ST-segment elevation suggestive of Brugada syndrome.
ARVC results from a genetic abnormality of right ventricular myocardium, replaced and infiltrated with fat and fibrous tissue.53 Patients may experience frequent PVCs and VT, resulting in syncope. Characteristic findings on a CT or MRI are fatty infiltration of the right ventricular myocardium. ECG may show complete or incomplete right bundle branch block, a juvenile T-wave pattern, or an epsilon wave. Major and minor criteria have been proposed to establish the diagnosis.(53) Patients with symptomatic ARVC should receive a defibrillator and frequently require antiarrhythmic medications (sotalol, amiodarone) to decrease the frequency of ICD shocks.
DRIVING AND SYNCOPE
Syncope while driving can have life-threatening consequences for operators, passengers, and other motorists. Patients with syncope are frequently instructed to refrain from driving until a definitive diagnosis is established and successful treatment assured. An expert consensus panel has summarized their suggestions based on specific syncope etiologies and the expected recurrence rates after appropriate therapy is implemented.54 In patients with vasovagal syncope, it is recommended that no driving be done for 3 months following what appears to be successful therapy. Patients with syncope due to VT who receive an ICD should refrain from private driving for an appropriate probationary period; approximately 6 or 7 months, as LOC can occur very quickly during VT before the ICD can detect, charge, shock, and terminate. Commercial driving is probably best avoided by patients with ICDs.
CONCLUSIONS
The evaluation of the patient with syncope requires a thoughtful and logical approach to avoid the pitfalls of unnecessary testing. Syncope in the presence of significant structural heart disease suggests a need for expedited hospitalized evaluation. If significant LV dysfunction is found, this frequently proceeds to a defibrillator. Neurocardiogenic or vasovagal syncope, although extremely common, remains a therapeutic challenge. Improved treatment modalities and pharmacologic interventions will require a better understanding of the epidemiology and pathophysiology. The role of tilt table testing in the evaluation of patients with syncope is evolving, and it is hoped that a uniformity of tilt table methodology and testing indications will soon be promulgated and adopted. The role of permanent pacemakers for vasovagal syncope remains uncertain. Improved monitoring technologies for syncope will enhance diagnostic capabilities. Implantable devices that monitor heart rate and blood pressure will greatly enhance the ability to diagnose patients accurately.
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QUESTIONS AND ANSWERS
Questions
1. An 83-year-old man comes to see you in your office complaining of three episodes of abrupt loss of consciousness (LOC) in the last year. His PMH is negative. His internist recently performed a stress echo test and Holter monitoring that were normal. His electrocardiography (ECG) reveals “trifascicular block.” What is the next step?
a. Perform electrophysiologic studies (EPS), and if negative, implant a Reveal device.
b. Perform EPS, and if negative, implant an implantable cardioverter-defibrillator (ICD).
c. Consider EPS for ventricular tachycardia (VT), and if negative, recommend a pacemaker.
d. Schedule a tilt test.
2. A 57-year-old man with dilated cardiomyopathy (DCM) presents to the emergency department with a facial laceration. He reports that he was urinating during the night and suddenly lost consciousness, falling and sustaining the injury. He felt fine before and after the event. He has an ejection fraction (EF) of 25% secondary to probable viral myocarditis. His ECG reveals IVCD and occasional multifocal PVCs. What is the next step?
a. Discharge from the emergency department with a 48-hour Holter monitor.
b. Admit, perform EPS, and if negative, implant a Reveal device.
c. Schedule an outpatient tilt test.
d. Admit, perform EPS, and if negative, offer an ICD.
3. A 21-year-old female college student presents to her local emergency department because she fainted twice earlier that day. She reports that the first episode occurred while she was in the shower. It was preceded by nausea with diaphoresis, followed by sudden LOC. After she awoke on the floor, she felt very nauseated, diaphoretic, and vomited. She tried to stand but fainted again. She is otherwise healthy but has had the “flu” for 3 days. You are asked to consult. Her PMH, ECG, physical exam, and lab are normal. She had previously fainted once, while donating blood at a blood drive. What tests should you order?
a. Tilt test
b. Holter monitoring
c. Stress echo test
d. None of the choices
4. Treatment for vasovagal syncope usually involves avoiding offending stimuli, dehydration, and prolonged standing; improving or decreasing venous pooling; and high-salt and high-fluid diet. For recurrent episodes, pharmacologic therapy is often employed. Initial pharmacologic therapy consists of all of the following except:
a. Beta-blockers
b. Disopyramide
c. Serotonin reuptake inhibitors
d. Florinef
5. Carotid sinus syndrome is probably the second most common cause of neurally mediated syncope. It results from hypersensitivity of the carotid reflex and causes marked bradycardia and, frequently, concomitant hypotension. All of the following are true regarding the features and treatment of carotid hypersensitivity except:
a. The finding of carotid sinus hypersensitivity is extremely specific for the presence of carotid sinus hypersensitivity and syndrome, and mandates pacemaker implantation.
b. Pacemaker implantation has been shown to significantly reduce the number of syncopal spells.
c. Patients with recurrent unexplained falls or injuries should be considered to have a neurally mediated syncopal etiology such as carotid sinus hypersensitivity and be tested either with carotid sinus massage testing or tilt table testing.
d. Carotid sinus hypersensitivity syndrome may result from abnormal proprioception and baroreceptor responses, in the carotid artery and the surrounding sternocleidomastoid.
6. A 20-year-old female college student, education major, presents complaining of recurrent dizziness, fatigue, light-headedness, palpitations, shortness of breath, and chest pain. This all began acutely several weeks ago. She was otherwise previously healthy and athletic. Her electrocardiogram shows normal sinus rhythm and heart rate in the 70s. During postural checks in the office, her heart rate goes to120 beats/min. Her physical exam is unremarkable although the patient is somewhat thin. What is the likely diagnosis?
a. Inappropriate sinus tachycardia
b. Vasovagal syncope
c. Hyperthyroidism
d. Postural orthostatic tachycardia syndrome
7. To confirm the diagnosis on the patient above, which of the following tests would not be initially performed?
a. Comprehensive blood work, CBC electrolytes, TSH
b. Electrophysiologic testing
c. Holter monitoring
d. Tilt table testing
8. A variety of pharmacologic and nonpharmacologic therapies have been proposed for patients with partial dysautonomia syndromes such as postural orthostatic tachycardia syndrome (POTS). Which of the following would not be an appropriate initial therapy?
a. 5 to 7 g sodium diet/commensurate with electrolytes/compression stockings
b. Graduated exercise program initially consisting of rowing machine, aqua therapy, recumbent bike
c. 4 to 6 inches elevation of the head of the bed
d. High-dose beta-blockade
9. A 79-year-old male presents following an episode of syncope while backing his car out of the driveway. He turned his head to look behind him, put the car in the motion, doesn’t recall what happened next and found himself on the lawn. The car was still running. There was no tongue biting or incontinence. He has no known arrhythmias but had an angioplasty without stenting years prior. His EKG shows normal sinus rhythm and is otherwise normal. An echo shows normal LV size and function. He is currently free of chest pain. Which of the following diagnoses are suggested by his history?
a. Acute myocardial infarction (MI)
b. Ventricular tachycardia
c. Carotid sinus syncope
d. Sick sinus syndrome
10. A 76-year-old male presents with recurrent syncope. His examination reveals supine hypertension and severe systolic and diastolic orthostatic hypotension (OH). He has no arrhythmias, no evidence of structural heart disease, but is relatively bradycardic. He has a history of Parkinson’s and takes Sinemet. Which of the following therapies are appropriate for initial treatment?
a. Thigh high or waist compression stockings
b. 4 to 6 inches elevation of the head of the bed
c. Physical therapy to improve orthostatic tolerance
d. Augmented fluid and salt
e. All of the choices
Answers
1. Answer C: The presence of trifascicular or bifascicular block on the ECG suggests that the underlying etiology of syncope may be intermittent heart block, Mobitz type II, third-degree heart block, the so-called Stokes–Adams block. Given a normal stress echo test and normal LV function, electrophysiologic testing will likely be negative for ventricular tachycardia. Based on current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, when no other cause for syncope is found, pacemaker implantation is indicated for syncope that has not been demonstrated to be due to AV block.
2. Answer D: Syncope in a patient with DCM is a very poor prognostic sign. Electrophysiologic testing has a low negative predictive value and therefore cannot be wholly relied on to screen patients who need a defibrillator. Implantation of a defibrillator remains a Class IIB indication in the presence of “advanced structural heart disease” denoting severe ischemic or nonischemic cardiomyopathy. In addition, based on the EF alone, the patient qualifies for ICD implantation according to the recent Definite and SCD-Heft data.
3. Answer D: Patients who present with a typical vasovagal episode with a classic prodrome and sequelae, who are otherwise healthy, probably require no other diagnostic testing or therapy, as the most unlikely etiology is vasovagal syncope. Tilt table testing is indicated only if the syncope becomes recurrent, or after single episodes of syncope with atypical features or for a high-risk patient.
4. Answer B: Disopyramide (Norpace) is a type IA sodium channel antiarrhythmic medication. It was proposed to be effective for vasovagal syncope based on its negative inotropic and anticholinergic effects. However, in a very well-designed study, using disopyramide loading and repeat tilt table tests, no efficacy was found. In addition, there is genuine concern for proarrhythmia in using the antiarrhythmic agents for treatment of a relatively benign disorder. Therefore, disopyramide may have a role for some patients, but it should not be used as initial therapy.
5. Answer A: Although the finding of carotid sinus hypersensitivity in a patient with recurrent syncope is highly suggestive, without the presence of the clinical syndrome the finding is relatively nonspecific. Carotid sinus hypersensitivity has been shown to be prevalent in patients with coronary disease and other forms of atherosclerotic disease as well. The sine qua non for carotid sinus syndrome is demonstration of carotid sinus hypersensitivity during carotid sinus massage, and a clinical scenario consistent with syncope resulting from direct stimulation of the carotid sinus baro and vagal reflex.
6. Answer D: POTS or postural orthostatic tachycardia syndrome is a poorly understood subacute dysautonomia with myriad symptoms, the hallmark of which is tachycardia with minimal exertion. Inappropriate sinus tachycardia, although possibly reflecting dysautonomia is frequently characterized by incessantly high heart rates. Although patients with POTS may be more susceptible to fainting, those solely with vasovagal propensity are usually not tachycardic.
7. Answer B: Electrophysiologic testing although frequently employed for documented or suspected supraventricular tachycardia (SVT) would not be revealing in patients with postural orthostatic tachycardia. Routine laboratory analysis, although frequently unremarkable, is certainly an appropriate component of initial evaluation of a patient with a sinus tachycardia syndrome. The sine qua non or gold standard for the diagnosis of postural orthostatic tachycardia is the tilt table test showing a heart rate increase of over 30 from baseline or over 120 beats within the first 10 minutes.
8. Answer D: Recent studies have supported the idea that nonpharmacologic approaches, particularly aggressive exercise programs are superior to medical therapy. Patients with orthostatic intolerance frequently do not tolerate beta-blockers, and if utilized, the dosage is ideally minimal.
9. Answer C: Syncope that occurs following movements of the head, pressure on the neck, Valsalva, etc., suggests the possibility of carotid sinus hypersensitivity which can be evaluated performing carotid sinus massage, in patients with no history of TIAs or cerebral vascular accidents (CVAs), and no carotid bruits. Carotid sinus hypersensitivity testing can reveal pauses of >3 seconds but can also reveal a vasodepressor reflex contributing to syncope. Carotid sinus syndrome is treated with a permanent pacemaker.
10. Answer E: The combination of supine hypertension and orthostatic hypotension is extremely clinically challenging scenario requiring multiple pharmacologic and nonpharmacologic interventions and extensive serial evaluation. Initial approaches as delineated above frequently can improve symptoms. However this syndrome tends to be progressive and ultimately requires pharmacologic approaches such as Florinef, and midodrine, which can be particularly problematic given the hypertension. Beta blockers may be helpful by leaving alpha receptors unopposed and actually improving vasoconstriction. However bradycardia can occur requiring permanent pacers. Patients with advanced central nervous system (CNS) disorders such as Parkinson’s may respond to Mestinon as well.