STATE-OF-THE-ART PAPER
SyncopeTherapeutic Approaches
David G. Benditt, MD* and
John T. Nguyen, MD, MPH
Cardiac Arrhythmia Center, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
Manuscript received October 2, 2008;
revised manuscript received December 1, 2008,
accepted December 15, 2008.
* Reprint requests and correspondence: Dr. David G. Benditt, Mail Code 508, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455 (Email: bendi001{at}umn.edu).
 |
Abstract
|
|---|
Syncope is a common clinical problem characterized by transient, spontaneously self-terminating loss of consciousness with complete and prompt recovery; the cause is insufficiency of cerebral oxygen/nutrient supply most often due to a transient fall of systemic arterial pressure to levels below those tolerated by cerebrovascular autoregulation. Careful and thorough evaluation of the cause of syncope is warranted in all patients. Determining that certain individuals are at "low mortality risk" is inadequate; syncope, although often benign from a mortality perspective, tends to recur, is associated with risk of physical injury, diminishes quality-of-life, and might lead to restriction from employment or avocation. However, the diagnostic evaluation and treatment of syncope is challenging for many reasons. First, syncope is only 1 of many causes of transient loss of consciousness. Second, the patient's symptoms are fleeting, and the patient is generally fully recovered when seen in the clinic; only infrequently are there helpful physical findings. Third, spontaneous events are often unwitnessed by medical professionals; consequently, the medical history of symptom events is usually a "second-hand" or "third-hand" story. Finally, there is often an excessive sense of diagnostic "urgency" that tends to result in a rush to undertake multiple poorly considered "diagnostic" testing procedures; a deliberate approach based on initial risk stratification is more likely to reap the dual rewards of a correct diagnosis and initiation of effective treatment in a cost-effective manner.
Key Words: cardiac arrhythmias • electrophysiology • hypotension • syncope
|
Abbreviations and Acronyms
| | ECG = electrocardiogram | | ED = emergency department | | EPS = electrophysiology study | | ICD = implantable cardioverter-defibrillator | | ILR = implantable (insertable) loop recorder | | NMS = neurally mediated syncope | | PCM = physical counter maneuvers | | RCT = randomized controlled trial | | TLOC = transient loss of consciousness | | SHD = structural heart disease | | SMU = syncope management unit |
|
The term "syncope" is derived from the Greek word "to cut short" or "interrupt"; its use as a descriptor of loss of consciousness has been traced back more than 600 years by editors of the Oxford English Dictionary. In this context, we can suppose that the link between the old Greek and current medical usage is the apparently temporary "interruption" of life's normal activities. However, in modern usage, "syncope" denotes a particular type of "interruption" in which: 1) loss of consciousness is temporary; 2) recovery is spontaneous, prompt, and complete; and 3) the cause is insufficiency of cerebral nutrient supply (1). A transient fall of systemic arterial pressure to levels below cerebrovascular autoregulation requirements is most often to blame. Other mechanisms, such as abrupt hypoxemic events (e.g., aircraft decompression), are rare.
In practical terms, patients who present with transient loss of consciousness (TLOC) describe their symptoms with words such as "collapse," "fall," or "black-out." In these cases, "syncope" is only 1 possibility; a broad range of potential causes for real or presumed TLOC must be considered. Thus, epilepsy, concussions, metabolic disturbances, intoxications, and "syncope mimics" (e.g., psychogenic pseudo-syncope, cataplexy) are also contenders; each differs from syncope with respect to both pathophysiology and treatment.
This review provides an overview for cardiologists of current thought regarding treatment to prevent syncope recurrences. However, therapy cannot be examined in isolation; therefore, consideration is also given to a strategy for the TLOC/syncope evaluation.
|
Diagnostic Approach
|
|---|
Thorough evaluation of the cause of syncope is warranted in all patients. This is important, because syncope, although perhaps benign from a mortality perspective in most cases, is rarely a solitary event; recurrences, physical injury, diminished quality-of-life, and possible lifestyle limitations are real concerns (2,3). Consequently, the goal must be to determine the cause of syncope with sufficient confidence to provide a reliable assessment of prognosis, recurrence risk, and treatment options (4).
Among the first questions to be addressed is whether to conduct the TLOC/syncope evaluation in-hospital or as an outpatient. Typical current practice patterns tend toward excessive in-hospital management. For instance, 1 recent report evaluated the frequency with which emergency department (ED) physicians elected hospital stay for evaluation of presumed syncope (5). Despite careful tutoring regarding European Society of Cardiology recommendations, there was a 25% inappropriate admission rate. Thus, many ED physicians remain concerned regarding the appropriateness of deferring syncope evaluations.
Potentially, greater use of "syncope management units" (SMUs), "rapid access blackout clinics" (6), or "TLOC/syncope clinics" might reduce inappropriate hospital admissions (7,8). For example, in the SEEDS (Syncope Evaluation in the Emergency Department Study) trial patients were randomized to "standard care" or SMU after initial ED assessment (an ED-based SMU was used to manage intermediate-risk patients for up to 6 h) (8). The frequency of presumptive diagnoses significantly increased from 10% in "standard care" patients to 67% with SMU evaluation, whereas both hospital admission frequency (98% to 43%) and total patient-hospital days (140 to 64 days) were less for SMU-managed patients. Furthermore, the SMU approach was more cost-efficient and equally as safe as the conventional strategy. Similarly, in the multicenter EGSYS-2 (Evaluation of Guidelines in Syncope Study 2) trial comparing "usual care" to guideline-based "standardized" care in the ED, the standardized group had a lower hospital stay rate (39% vs. 47%, p = 0.001), shorter hospital stays (approximately 1 day less), fewer diagnostic tests (2.6 vs. 3.4, p = 0.001), and an approximately 20% lower overall cost (7). For EDs without an SMU, an observation unit similar to that used for "chest pain" assessment might prove useful.
Apart from more widespread application of SMUs, development of effective criteria for determining which patients require in-hospital evaluation would also reduce unnecessary admissions. However, despite many proposals (see Table 1
for selected examples) (1,8–13), none are perfect. For instance, the STePS (Short-Term Prognosis of Syncope) study suggested that an abnormal electrocardiogram (ECG), trauma, absence of warning, and male sex were markers of short-term (<10 days) adverse outcomes and therefore warranted hospital stay (9). However, an accompanying editorial argued that the STePS study's positive predictive value for separating high- from low-risk patients was too small to be useful (10). Similarly, attempts to validate other suggested stratification techniques have led to variable outcomes. For instance, the ROSE (Risk stratification Of Syncope in the Emergency department) study (14) found that clinical judgment was just as accurate as application of the San Francisco Rule (11) for reducing unneeded hospital admissions.
Our recommendations (Table 2) regarding the need for hospital stay of patients with presumed syncope are derived from the reports in Table 1. In general, hospital admission is prudent if the suspected underlying problem is associated with high risk of early mortality or injury, the proposed treatment requires in-hospital care, or the affected individual is unable to care for himself or herself.
|
Syncope Classification and Diagnostic Tools
|
|---|
An accurate diagnosis is the essential foundation for effective treatment of syncope patients (Table 3). However, despite a well-organized and thorough approach to establishing a syncope diagnosis (Fig. 1), often it is not possible to assign a single cause. Multiple comorbidities are common. Thus, individuals with heart disease might faint due to transient tachyarrhythmias, high-grade atrioventricular block, or overmedication. The physician should not too quickly accept an observed abnormality to be causal in a given individual.
View larger version (36K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1 Initial Approach to the Evaluation of Suspected Syncope
Diagnostic pathway for evaluation of suspected syncope (see the Syncope Classification and Diagnostic Tools section for details). The approach advocated here is modified from that proposed in the European Society of Cardiology syncope guidelines. AECG = ambulatory electrocardiogram; CSM = carotid sinus massage; ECG = electrocardiogram; Echo = echocardiogram; EP = electrophysiologic; ILR = implantable loop recorder; Rx = treatment; SHD = structural heart disease.
|
|
The most valuable tools for establishing the basis of syncope are a careful medical history aided by eyewitness reports (1,15,16) and physical findings addressing the presence of structural heart disease (SHD). It has been reported that SHD independently predicts a cardiac cause of syncope with 95% sensitivity and 45% specificity (17). Likewise, the absence of SHD excluded cardiac syncope in 97% of patients. Table 4
provides a summary of key findings that suggest a cardiac origin for syncope.
The 12-lead ECG and echocardiogram are essential elements of the initial syncope evaluation. Although it is rare that either provides a definitive diagnosis, they might facilitate choice of subsequent tests. For instance, ECG findings summarized in Table 5
or echocardiographic findings of unsuspected left ventricular dysfunction, dynamic ventricular outflow obstruction, or atrial myxoma/thrombus might provide valuable clues.
Extended-duration continuous ECG monitoring with either mobile cardiac outpatient telemetry (18) or an implantable loop recorder (ILR) (19–22) has proved valuable for determining the cause(s) of syncope when events occur infrequently. For example, the RAST (Randomized Assessment of Syncope Trial) demonstrated that a primary ILR diagnostic strategy was twice as effective as a "conventional" work-up composed of 2 to 4 weeks of an external ECG loop recorder, provocative tilt-table testing, and electrophysiologic study (EPS) (19). The EaSyAS (Eastbourne Syncope Assessment Study) came to a similar conclusion (20). Both showed substantial ILR cost/diagnosis benefit.
Other tests, including tilt-table testing, EPS, and cardiac hemodynamic evaluation, should be chosen only when the initial evaluation supports their use (Fig. 1). Indications for EPS in syncope patients and findings that might help to define a basis for syncope are summarized in Tables 6 and 7. Neurological tests (e.g., electroencephalography and head computed tomography or magnetic resonance imaging) are almost never of value, absent concern regarding potential intracranial injury (e.g., subdural hematoma) that might have been sustained due to a fall.
|
Treatment of Specific Types of Syncope
|
|---|
Currently, treatment of syncope patients relies primarily on clinical experience and observational reports. The principal exceptions are vasovagal syncope and to a lesser degree orthostatic hypotension.
Neurally mediated reflex syncopal syndromes.
Patient education is the foundation of treatment of most neurally mediated syncope (NMS) syndromes. Patients must be informed that, although reflex faints are almost never life-threatening (1,23), they tend to recur (often in clusters), and injury can result if preventive measures are not taken seriously. Furthermore, patients might benefit by some understanding of basic pathophysiology and the importance of recognizing and responding to warning symptoms; such understanding not only reduces injury risk but also might ultimately enhance treatment compliance. In addition, it is important to identify and treat psychological and/or psychiatric factors that might contribute to exacerbating symptom susceptibility. In this regard, a high prevalence of minor psychiatric disorders has been reported in patients with vasovagal syncope (24,25).
Recurrent vasovagal fainters should learn techniques for aborting imminent attacks and reducing susceptibility to future attacks (e.g., physical maneuvers, liberalized salt intake, hydration). They should also be taught the value and possible risks of increased salt intake. In situational faints, it might be possible to ameliorate or avoid triggers. For instance, one might target cough suppression and smoking cessation in "cough syncope" and sitting while voiding in "micturition syncope." In some cases (e.g., syncope associated with fear of air flight), desensitization techniques might help.
Carotid sinus syndrome is a special form of NMS (1,26) that tends to occur in older individuals and predisposes them to falls and injury (26). In such cases, although avoidance of tight collars, neckties, and abrupt neck movements is prudent advice, early initiation of cardiac pacing is usually recommended (1,27,28).
As alluded to earlier, physical counter-pressure maneuvers (PCM) are increasingly advocated to abort imminent NMS or orthostatic faints in patients who are aware of warning symptoms. Thus, squatting, arm-tensing, leg-crossing, and leg-crossing with lower body muscle tensing have proved useful for averting an abrupt vasovagal reaction (29,30) (Fig. 2). In the PC-Trial (Physical Counterpressure Manoeuvres Trial), PCM reduced total burden and recurrence rate of syncopal events (31). In brief, "usual" therapy plus PCM was compared with "usual" therapy alone in patients with recognizable warning symptoms. The syncope burden during follow-up was lower in PCM-trained patients versus control subjects; overall, 32% of PCM-trained and 51% of conventional arm patients experienced syncope recurrence (p < 0.005). Recurrence-free survival was better with PCM (39% relative risk reduction). Consequently, PCM should be part of the treatment strategy in patients with warning symptoms.
View larger version (22K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Physical Maneuvers to Counter an Imminent Vasovagal or Orthostatic Faint
Schematics illustrating physical counter-maneuvers designed to delay an imminent vasovagal or orthostatic faint. Each of these maneuvers might boost blood pressure sufficiently to delay symptoms. The objective is to "buy time" during which the affected individual can seek a safe haven. (A) The subject is depicted using leg-crossing with lower body muscle tensing (left) or squatting (right) to enhance blood pressure. (B) Arm-tensing is illustrated. Figure illustrations by Rob Flewell.
|
|
Strategies for reducing syncope recurrences in the long-term comprise: 1) physical techniques to improve orthostatic tolerance; 2) pharmacologic interventions to prevent depletion of intravascular volume and/or enhance arterial and venous tone; and 3) cardiac pacing to avert bradycardia.
Physical Techniques
The goal of "tilt-training" (more accurately termed "standing-training") is to enhance neurovascular response to orthostatic stress (32) (Fig. 3). Initially the "tilt-training" concept used repeated in-hospital exposure to postural stress by tilt-table tests until syncope was no longer inducible. However, this approach is impractical. Currently, the method entails home "standing-training" for progressively longer periods of time over 10 to 12 weeks. At the beginning, the recommended standing duration is 3 to 5 min twice daily; standing duration is then gradually lengthened every 3 to 4 days to as much as 30 to 40 min twice daily.
View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 Tilt-Training (Standing-Training)
Schematic illustrating the "tilt-training" technique for home use. Patients are instructed to stand and place only the upper back against a wall (with ankles approximately 15 cm away from the wall) without moving. The sessions are initially performed in a quiet and comfortable environment (possibly under supervision of a family member). The patient stands still with upper back positioned lightly against a wall or a corner. A carpeted floor is preferred, and the nearby environment should be devoid of sharp-edged objects or other hazards should the patient fall. Initially we recommend 3 to 5 min of standing twice daily. Then, depending on symptom status, the duration can be slowly increased each week. The target is 20 to 30 min twice daily without symptoms. Thereafter, 20 min sessions 3 to 4 times/week are recommended indefinitely. Figure illustration by Rob Flewell.
|
|
Nonrandomized studies suggest that tilt-training reduces NMS susceptibility if undertaken consistently (33–35). However, compliance is a limitation, and randomized observations have been less encouraging (36). Further studies are needed.
Pharmacotherapy
A number of drugs, including "over-the-counter" remedies of uncertain composition and safety, are commonly prescribed for prevention of NMS. However, there are few randomized clinical trials, and consequently no agent, excepting perhaps midodrine, can be said to have proven effectiveness.
Volume expansion has been the foundation of medical therapy for both vasovagal faints and orthostatic syncope (discussed in later text). Conventional approaches to volume expansion entail increased dietary salt and electrolyte-rich sport drinks (although it is wise to avoid many high-caloric "sport" drinks) (37). The primary safety concern is induction of hypertension. This is uncommon in younger patients but is a greater concern in older patients.
Among prescription drugs for volume expansion, fludrocortisone (a synthetic mineralocorticoid) is the most widely used, especially in younger patients (38). Side effects include hypertension and hypokalemia. However, clinical evidence of fludrocortisone efficacy is weak. For instance, in adolescents, Scott et al. (39) demonstrated no benefit over atenolol in preventing recurrence of syncope in a randomized trial. Similarly, Salim and Di Sessa (40) found fludrocortisone to be less effective than placebo in preventing syncope or pre-syncope in children. A larger randomized controlled trial (RCT) with fludrocortisone in vasovagal syncope is ongoing (POST II [Second Prevention of Syncope Trial]) (41).
Among other drug classes proposed for prevention of vasovagal faints, the beta-adrenoceptor antagonists (beta-blockers) were thought to reduce susceptibility by diminishing the impact of the adrenergic surge that commonly precedes and might be part of the trigger (15,42–44). However, supportive evidence is derived largely from observational reports and a single small RCT (45). More recently a relatively large RCT (POST [Prevention of Syncope Trial]) showed no clear beta-blocker benefit in terms of syncope recurrence prevention (46). In the POST trial, 208 patients with >2 syncopal events each were randomized to treatment with metoprolol or placebo. During a 1-year follow-up syncope recurrence was similar in both groups. However, somewhat surprisingly, older metoprolol-treated patients (age >42 years) seemed to show some benefit, albeit not statistically significant.
Vasoconstrictors and venoconstrictors have also been of interest in this setting. Etilephrine, a modest alpha- and beta-agonist, was studied in the VASIS (Vasovagal International Study) but did not prove effective (47). Currently, midodrine is the principal vasoconstrictor for this indication. Midodrine is a pro-drug, metabolized in the liver to the active agent, desglymidodrine, which acts to constrict both arterial and venous beds, thus increasing peripheral blood pressure, improving venous return, and diminishing venous pooling. Midodrine has been most extensively studied in patients with orthostatic hypotension (48) but has also been shown to be effective in vasovagal syncope (49,50). Midodrine only infrequently causes hypertension, but it might precipitate urinary retention or urgency in older men and occasionally induces scalp "tingling" presumably due to piloerector muscle contraction. Methylphenidate has been proposed as an alternative for midodrine-intolerant patients (51); however, its value has not been established. Furthermore, unlike midodrine, methylphenidate crosses the blood brain barrier and can cause multiple adverse effects (e.g., agitation, movement disturbances, irritability).
Finally, several other drugs have been advocated but at best remain of uncertain effectiveness. Foremost among these are selective serotonin reuptake inhibitors (52). It has been postulated that an abnormal hypersensitive serotonin response in the central nervous system contributes to triggering NMS; selective serotonin reuptake inhibitor pre-treatment is thought to blunt this abnormal response. However, although 1 RCT showed reduced syncope recurrence in 30 patients taking active medication compared with placebo (53), a subsequent study showed no benefit (54). Other agents—disopyramide, pure anticholinergics (e.g., scopolamine), and theophylline—have also been proposed, but the reported experience for any of these is small, uncontrolled, and currently unconvincing.
Cardiac Pacing
As noted earlier, cardiac pacing has long been considered an essential part of the treatment of carotid sinus syndrome (26,27,55,56). However, the role of pacing in patients with "refractory" vasovagal syncope is less certain. The proposed mode of benefit is thought to be prevention of severe bradycardia (cardio-inhibitory syncope). However, although 3 unblinded RCTs (the VPS [North American Vasovagal Pacemaker Study] [57], the VASIS trial [47], and the SYDIT [Syncope Diagnosis and Treatment] study [58]) showed efficacy for pacing, 2 subsequent trials in which pacemakers were present in both treatment arms (VPS II [Second Vasovagal Pacemaker Study] [59] and SYNPACE [Vasovagal Syncope and Pacing Trial] [60]) did not show benefit. A larger ongoing multicenter study (ISSUE-3 [International Study on Syncope of Uncertain Etiology 3] [61]) is addressing some of the shortcomings of prior studies, but results will not be available for 2 to 3 years. Until then, cardiac pacing is recommended only for older vasovagal fainters with documented symptomatic asystolic pauses during spontaneous faints (e.g., documented by ILR).
Orthostatic syncope and related autonomic disturbances.
Orthostatic syncope results from an excessive fall of systemic pressure (hypotension) triggered by postural change (e.g., supine or sitting to upright posture). In quantitative terms, clinically significant orthostatic hypotension is defined as a reduction of systolic blood pressure of  20 mm Hg and/or a diastolic fall of 10 mm Hg within 3 min of standing, regardless of whether symptoms occur.
Orthostatic hypotension might be caused by: 1) impaired capacity of sympathetic nerves to increase vascular resistance due to primary nervous system disease or secondary to other diseases or drugs (or toxins) that adversely affect the autonomic nervous system; 2) relative volume depletion; 3) downward pooling of venous blood and a consequent reduction in stroke volume and cardiac output; or 4) impaired cardiac diastolic relaxation, especially of the aged or hypertrophied heart. Orthostatic syncope might be due specifically to: 1) primary autonomic neurological disturbance (e.g., pure autonomic failure, multiple system atrophy, Parkinson's disease); 2) drugs (e.g., vasodilators, diuretics); or 3) acquired disease (e.g., diabetes, alcohol, and so on) (62,63). Prevention is often difficult. When caused by a primary autonomic disease process, progress can often be made slowly if the patient is persistent with therapy, but complete return to "normal" is not a reasonable expectation. The best case is orthostatic syncope caused by nonessential drugs that can be eliminated.
Treatment of orthostatic syncope parallels the strategy discussed earlier for vasovagal and situational faints, with certain differences: 1) the duration of treatment is likely to be longer; 2) affected individuals are typically older and frailer, making PCM more difficult to employ; and 3) patients are more prone to supine hypertension.
Treatment should focus initially on education about factors that aggravate or provoke postural hypotension (Table 8). Thereafter, patients should be advised regarding maintenance of hydration (volume expanders are encouraged with careful follow-up to avoid excessive hypertension) as discussed in the reflex syncope section, PCM (Fig. 2), and "tilt-training" (Fig. 3). Furthermore, patients with autonomic failure should be advised to sleep with the head of the bed somewhat elevated (approximately 20 to 25 cm). Finally, vasoconstrictors such as midodrine (see the preceding text) might be introduced. However, fluctuating blood pressures and supine hypertension are often encountered. In such cases it is essential to try to tailor timing of therapy to support the arterial pressure during daytime and to prevent hypertension at night (while also minimizing risk of falling when affected individuals get out of bed in the middle of the night).
A special case is the patient with severe pure autonomic failure. In these individuals, bolus water intake, especially before rising from bed in the morning, might result in a valuable increase in blood pressure (64). This technique might also be worth trying in other patients with postural hypotension in whom symptoms are often most troublesome in the morning (after prolonged absence of oral intake and increased supine renal filtration).
Other agents advocated for treatment of orthostatic hypotension in specialized circumstances include erythropoietin (65,66), clonidine (67), octreotide (68), and desmopressin (69). However, evidence supporting each of these is marginal.
Cardiac arrhythmias as primary cause of syncope.
Determining that a specific cardiac arrhythmia is responsible for syncope remains a diagnostic challenge. The initial evaluation might provide clues, but selected diagnostic tests are usually required. Long-term ECG monitoring is often warranted. In this regard, among wearable ECG event recorders, mobile cardiac outpatient telemetry devices have been shown to be superior to conventional event recorders in syncope patients (18). Additionally, the ISSUE study illustrated, in terms of implantable monitors, the diagnostic value of ILRs in syncope patients, in particular for those with underlying evidence of conduction system disease (70) or SHD (71). In the former case, bradyarrhythmias tended to predominate, whereas in the latter, the detected arrhythmias were more heterogeneous. In some instances but not often, EPS is needed (Table 6). Apart from its diagnostic value, invasive EPS also offers the potential to cure certain arrhythmias by transvenous catheter ablation, a technique now available in most EPS laboratories.
In the case of cardiac arrhythmias being the primary cause of syncope, treatment decisions are directed at the specific documented arrhythmia (1). Cardiac pacemakers are highly effective for bradyarrhythmias, whether due to underlying conduction system disease or, as is often the case in older patients, the effects of essential drug therapy (e.g., beta-blockers, anti-arrhythmic drugs). Tachyarrhythmic origins of syncope often lead to consideration of EPS mapping and ablation. For example, ablation is usually recommended as initial therapy for many supraventricular tachycardias and ventricular tachycardias of right or left ventricular outflow tract origin or due to bundle-branch re-entry. The effectiveness of ablation in paroxysmal atrial fibrillation causing syncope is less certain. In some cases, His bundle ablation with permanent pacing might be a valuable back-up option.
Absent the possibility of a curative ablation procedure, it is often necessary to use combinations of antiarrhythmic drugs along with implanted devices (pacemakers or implantable cardioverter-defibrillators [ICDs]). Thus, in patients with certain channelopathies (e.g., long QT syndrome, Brugada syndrome, short QT syndrome), the life-threatening risk is often too great to rely on medications alone (e.g., beta-blockade in some long QT syndrome patients), and an ICD is recommended. However, ICDs alone might not prevent syncope, due to the time taken to diagnose the arrhythmia and initiate treatment. For instance, in an examination of data gleaned from SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), rates of syncope did not differ between the 3 treatment arms (ICD, amiodarone, placebo) (72).
Structural cardiovascular and cardiopulmonary disease.
Most often, syncope associated with SHD is secondary to either neurally mediated reflex mechanisms (e.g., acute myocardial ischemia) or primary arrhythmias, both of which have been discussed in the preceding text. In certain cases, however, hemodynamic studies reveal abnormalities of sufficient severity to indicate that SHD is directly responsible (e.g., severe aortic stenosis or mitral stenosis or obstructive HCM). In such instances, symptom prevention is best achieved by ameliorating the primary structural disturbance if possible. Thus, severe valvulopathies require surgery, whereas obstructive HCM can often be managed with drugs and possibly cardiac pacing (73). In other circumstances, however, currently available interventions cannot provide adequate protection; pulmonary hypertension might be the most important example.
Cerebrovascular syncope.
Migraines due to vascular spasm might be the most important cause of syncope in this section; however, this mechanism must be rare, because it would require simultaneous multivessel involvement. More likely, the origin of faints in migraineurs might be related to an element of associated autonomic dysfunction (74) and in particular vasovagal events triggered by pain and nausea. In any case, the medical management includes use of beta-blockers and cranial/basilar artery vasoconstrictors such as sumatriptan (75). Subclavian steal syndrome is another condition in this category that might cause faints, but these are very rare; its treatment requires either surgical or catheter-based intervention (76).
Structural cerebrovascular disease might cause strokes and transient ischemic attacks but is almost never the cause of syncope. One very infrequent exception might be vertebrobasilar transient ischemic attacks, but these are usually accompanied by other posterior circulation symptoms such as vertigo. The treatment of transient ischemic attacks lies outside the boundaries of this review.
|
Conclusions
|
|---|
The evaluation and treatment of syncope is challenging. First, "syncope" is only one of many causes of TLOC. Second, symptoms are fleeting, and the patient is usually asymptomatic when seen in the clinic. Third, events are often unwitnessed; but even when witnessed, the stress of the moment might undermine reliability of the account. Finally, there is often an excessive sense of diagnostic "urgency"; this results in a rush to undertake multiple poorly considered "diagnostic" testing procedures. A deliberate approach based on initial risk stratification is more likely to reap the reward of a correct diagnosis.
Despite the difficulties, a thorough evaluation of the cause of syncope is warranted in all patients—not just in those deemed to be at high mortality risk. Conversely, the mere presence of an abnormal finding does not constitute a "diagnosis." The physician must carefully consider whether detected abnormalities are compatible with the clinical circumstances. The goal in every case should be to determine the cause with sufficient confidence to provide a reliable assessment of prognosis and treatment options.
|
Acknowledgments
|
|---|
The authors would like to thank the many members of both the European Society of Cardiology Syncope Guidelines Task Force and the "Ad Hoc" Syncope Consortium who, through the course of numerous discussions, have contributed immeasurably to the concepts summarized in this document. We also acknowledge Mr. Rob Flewell, CMI, for his invaluable assistance with the figures.
|
Footnotes
|
|---|
Dr. Benditt is a consultant to and has equity in Medtronic, Inc., St. Jude Medical, Cardionet, Inc., and Transoma, Inc., manufacturers of diagnostic instruments and implantable devices used to evaluate and treat certain syncope patients.
|
References
|
|---|
1. Brignole M, Alboni P, Benditt DG, et al. Guidelines on management (diagnosis and treatment) of syncope—update 2004 Europace 2004;6:467-537.[Free Full Text]2. Bartoletti A, Fabiani P, Bagnoli L, et al. Physical injuries caused by a transient loss of consciousness: main clinical characteristics of patients and diagnostic contribution of carotid sinus massage Eur Heart J 2008;29:618-624.[Abstract/Free Full Text] 3. Davies AJ, Kenny RA. Falls presenting to the accident and emergency department: types of presentation and risk factor profile Age Ageing 1996;25:362-366.[Abstract/Free Full Text] 4. Benditt DG, Olshansky B, Wieling W, Ad Hoc Syncope Consortium The ACCF/AHA scientific statement on syncope needs rethinking J Am Coll Cardiol 2006;48:2598-2599.[Free Full Text] 5. Bartoletti A, Fabiani P, Adriani P, et al. Hospital admission of patients referred to the emergency department for syncope: a single-hospital prospective study based on the application of the European Society of Cardiology Guidelines on Syncope Eur Heart J 2006;27:83-88.[Abstract/Free Full Text] 6. Petkar S, Bell W, Rice N, Iddon P, Cooper P, Fitzpatrick A. Rationale for a rapid access blackouts triage clinic Brit J Cardiac Nursing 2008;10:468-474. 7. Brignole M, Ungar A, Bartoletti A, et al. Standardized-care pathway vs. usual management of syncope patients presenting as emergencies at general hospitals Europace 2006;8:644-650.[Abstract/Free Full Text] 8. Shen WK, Decker WW, Smars PA, et al. Syncope Evaluation in the Emergency Department study (SEEDS): a multidisciplinary approach to syncope management Circulation 2004;110:3636-3645.[Abstract/Free Full Text] 9. Costantino G, Perego F, Dipaola F, et al. Short- and long-term prognosis of syncope, risk factors, and role of hospital admission: results from the STePS (short-term prognosis of syncope) study J Am Coll Cardiol 2008;51:276-283.[Abstract/Free Full Text] 10. Brignole M, Shen WK. Syncope management from emergency department to hospital J Am Coll Cardiol 2008;51:284-287.[Free Full Text] 11. Quinn JV, Stiell IG, McDermott DA, Sellers KL, Kohn MA, Wells GA. Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes Ann Emerg Med 2004;43:224-232.[CrossRef][Web of Science][Medline] 12. Colivicchi F, Ammirati F, Melina D, et al. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score Eur Heart J 2003;24:811-819.[Abstract/Free Full Text] 13. Del Rosso A, Ungar A, Maggi R, et al. Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to general hospital: the EGSYS score Heart 2008;94:1620-1626.[Abstract/Free Full Text] 14. Reed MJ, Newby DE, Coull AJ, Jacques KG, Prescott RJ, Gray AJ. The Risk stratification Of Syncope in the Emergency department (ROSE) pilot study: a comparison of existing syncope guidelines Emergency Med J 2007;24:270-275.[CrossRef] 15. Kapoor WN. Diagnostic evaluation of syncope Am J Med 1991;90:91-106.[CrossRef][Web of Science][Medline] 16. Calkins H, Shyr Y, Frumin H, Schork A, Morady F. The value of the clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope Am J Med 1995;98:365-373.[CrossRef][Web of Science][Medline] 17. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease J Am Coll Cardiol 2001;37:1921-1928.[Abstract/Free Full Text] 18. Rothman SA, Laughlin JC, Seltzer J, et al. The diagnosis of cardiac arrhythmias: a prospective multi-center randomized study comparing mobile cardiac outpatient telemetry versus standard loop event monitoring J Cardiovasc Electrophysiol 2007;18:241-247.[CrossRef][Web of Science][Medline] 19. Krahn AD, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy Circulation 2001;104:46-51.[Abstract/Free Full Text] 20. Farwell DJ, Freemantle N, Sulke AN. Use of implantable loop recorders in the diagnosis and management of syncope Eur Heart J 2004;25:1257-1263.[Abstract/Free Full Text] 21. Moya A, Brignole M, Menozzi C, et al. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope Circulation 2001;104:1261-1267.[Abstract/Free Full Text] 22. Brignole M, Sutton R, Menozzi C, et al. Early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected neurally mediated syncope Eur Heart J 2006;27:1085-1092.[Abstract/Free Full Text] 23. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope N Engl J Med 2002;347:878-885.[CrossRef][Web of Science][Medline] 24. Giada F, Silvestri I, Rossillo A, Nicotera PG, Manzillo GF, Raviele A. Psychiatric profile, quality of life and risk of syncopal recurrence in patients with tilt-induced vasovagal syncope Europace 2005;7:465-471.[Abstract/Free Full Text] 25. Leftheriotis D, Michopoulos I, Flevari P, et al. Minor psychiatric disorders and syncope: the role of psychopathology in the expression of vasovagal reflex Psychother Psychosom 2008;77:372-376.[CrossRef][Web of Science][Medline] 26. Almquist A, Gornick C, Benson Jr. DW, Dunnigan A, Benditt DG. Carotid sinus hypersensitivity: evaluation of the vasodepressor component Circulation 1985;71:927-936.[Abstract/Free Full Text] 27. Kenny RA, Richardson DA, Steen N, Bexton RS, Shaw FE, Bond J. Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE) J Am Coll Cardiol 2001;38:1491-1496.[Abstract/Free Full Text] 28. Epstein AE, Baessler CA, Curtis AB, et al. Addendum to public safety issues in patients with implantable defibrillators: a scientific statement from the American Heart Association and the Heart Rhythm Society Circulation 2007;115:1170-1176.[Abstract/Free Full Text] 29. Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W. Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing Circulation 2002;106:1684-1689.[Abstract/Free Full Text] 30. Brignole M, Croci F, Menozzi C, et al. Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope J Am Coll Cardiol 2002;40:2053-2059.[Abstract/Free Full Text] 31. van Dijk N, Quartieri F, Blanc JJ, et al. Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: the Physical Counterpressure Manoeuvres Trial (PC-Trial) J Am Coll Cardiol 2006;48:1652-1657.[Abstract/Free Full Text] 32. Ector H, Reybrouck T, Heidbuchel H, Gewillig M, Van de Werf F. Tilt training: a new treatment for recurrent neurocardiogenic syncope and severe orthostatic intolerance Pacing Clin Electrophysiol 1998;21:193-196.[CrossRef][Medline] 33. Di Girolamo E, Di Iorio C, Leonzio L, Sabatini P, Barsotti A. Usefulness of a tilt training program for the prevention of refractory neurocardiogenic syncope in adolescents: a controlled study Circulation 1999;100:1798-1801.[Abstract/Free Full Text] 34. Reybrouck T, Heidbuchel H, Van De Werf F, Ector H. Long-term follow-up results of tilt training therapy in patients with recurrent neurocardiogenic syncope Pacing Clin Electrophysiol 2002;25:1441-1446.[CrossRef][Medline] 35. Kinay O, Yazici M, Nazli C, et al. Tilt training for recurrent neurocardiogenic syncope: effectiveness, patient compliance, and scheduling the frequency of training sessions Jpn Heart J 2004;45:833-843.[CrossRef][Medline] 36. Gurevitz O, Barsheshet A, Bar-Lev D, et al. Tilt training: Does it have a role in preventing vasovagal syncope? Pacing Clin Electrophysiol 2007;30:1499-1505.[Medline] 37. El-Sayed H, Hainsworth R. Salt supplement increases plasma volume and orthostatic tolerance in patients with unexplained syncope Heart 1996;75:134-140.[Abstract/Free Full Text] 38. Parry SW, Kenny RA. The management of vasovagal syncope QJM 1999;92:697-705.[Free Full Text] 39. Scott WA, Pongiglione G, Bromberg BI, et al. Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope Am J Cardiol 1995;76:400-402.[CrossRef][Web of Science][Medline] 40. Salim MA, Di Sessa TG. Effectiveness of fludrocortisone and salt in preventing syncope recurrence in children: a double-blind, placebo-controlled, randomized trial J Am Coll Cardiol 2005;45:484-488.[Abstract/Free Full Text] 41. Raj SR, Rose S, Ritchie D, Sheldon RS, POST II Investigators The Second Prevention of Syncope Trial (POST II)—a randomized clinical trial of fludrocortisone for the prevention of neurally mediated syncope: rationale and study design Am Heart J 2006;151:1186.e1-1186.e7.[CrossRef][Medline] 42. Muller G, Deal BJ, Strasburger JF, Benson Jr DW. Usefulness of metoprolol for unexplained syncope and positive response to tilt testing in young persons Am J Cardiol 1993;71:592-595.[CrossRef][Web of Science][Medline] 43. Cohen MB, Snow JS, Grasso V, et al. Efficacy of pindolol for treatment of vasovagal syncope Am Heart J 1995;130:786-790.[CrossRef][Web of Science][Medline] 44. Iskos D, Dutton J, Scheinman MM, Lurie KG. Usefulness of pindolol in neurocardiogenic syncope Am J Cardiol 1998;82:1121-1124A9.[CrossRef][Web of Science][Medline] 45. Mahanonda N, Bhuripanyo K, Kangkagate C, et al. Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results Am Heart J 1995;130:1250-1253.[CrossRef][Web of Science][Medline] 46. Sheldon R, Connolly S, Rose S, et al. Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope Circulation 2006;113:1164-1170.[Abstract/Free Full Text] 47. Sutton R, Brignole M, Menozzi C, et al. Vasovagal Syncope International Study (VASIS) Investigators Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope: pacemaker versus no therapy Circulation 2000;102:294-299.[Abstract/Free Full Text] 48. Jankovic J, Gilden JL, Hiner BC, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine Am J Med 1993;95:38-48.[CrossRef][Web of Science][Medline] 49. Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope Heart 1998;79:45-49.[Abstract/Free Full Text] 50. Perez-Lugones A, Schweikert R, Pavia S, et al. Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study J Cardiovasc Electrophysiol 2001;12:935-938.[CrossRef][Web of Science][Medline] 51. Grubb BP, Kosinski D, Mouhaffel A, Pothoulakis A. The use of methylphenidate in the treatment of refractory neurocardiogenic syncope Pacing Clin Electrophysiol 1996;19:836-840.[CrossRef][Medline] 52. Grubb BP, Wolfe DA, Samoil D, Temesy-Armos P, Hahn H, Elliott L. Usefulness of fluoxetine hydrochloride for prevention of resistant upright tilt induced syncope Pacing Clin Electrophysiol 1993;16:458-464.[CrossRef][Medline] 53. Di Girolamo E, Di Iorio C, Leonzio L, Sabatini P, Ranalli G, Barsotti A. Effectiveness of paroxetine in the treatment of refractory vasovagal syncope in young patients G Ital Cardiol 1999;29:1472-1477.[Medline] 54. Takata TS, Wasmund SL, Smith ML, et al. Serotonin reuptake inhibitor (paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers Circulation 2002;106:1500-1504.[Abstract/Free Full Text] 55. Brignole M, Menozzi C, Lolli G, Bottoni N, Gaggioli G. Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome Am J Cardiol 1992;69:1039-1043.[CrossRef][Web of Science][Medline] 56. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons J Am Coll Cardiol 2008;51:e1-e62.[Free Full Text] 57. Connolly SJ, Sheldon R, Roberts RS, Gent M. The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol 1999;33:16-20.[Abstract/Free Full Text] 58. Ammirati F, Colivicchi F, Santini M, Syncope Diagnosis and Treatment Study Investigators Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter, randomized, controlled trial Circulation 2001;104:52-57.[Abstract/Free Full Text] 59. Connolly SJ, Sheldon R, Thorpe KE, et al. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial JAMA 2003;289:2224-2229.[Abstract/Free Full Text] 60. Raviele A, Giada F, Menozzi C, et al. A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The Vasovagal Syncope and Pacing Trial (SYNPACE). Eur Heart J 2004;25:1741-1748.[Abstract/Free Full Text] 61. Brignole M. International Study on Syncope of Uncertain Aetiology 3 (ISSUE 3): pacemaker therapy for patients with asystolic neurally-mediated syncope: rationale and study design Europace 2007;9:25-30.[Abstract/Free Full Text] 62. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients Lancet 2001;357:348-353.[CrossRef][Web of Science][Medline] 63. Mathias CJ. Autonomic diseases: clinical features and laboratory evaluation J Neurol Neurosurg Psychiatry 2003;74(Suppl 3):iii31-iii41.[Free Full Text] 64. Young TM, Mathias CJ. The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure J Neurol Neurosurg Psychiatry 2004;75:1737-1741.[Abstract/Free Full Text] 65. Hoeldtke RD, Streeten DH. Treatment of orthostatic hypotension with erythropoietin N Engl J Med 1993;329:611-615.[CrossRef][Web of Science][Medline] 66. Kawakami K, Abe H, Harayama N, Nakashima Y. Successful treatment of severe orthostatic hypotension with erythropoietin Pacing Clin Electrophysiol 2003;26:105-107.[CrossRef][Medline] 67. Robertson D, Goldberg MR, Hollister AS, Wade D, Robertson RM. Clonidine raises blood pressure in severe idiopathic orthostatic hypotension Am J Med 1983;74:193-200.[CrossRef][Web of Science][Medline] 68. Hoeldtke RD, Israel BC. Treatment of orthostatic hypotension with octreotide J Clin Endocrinol Metab 1989;68:1051-1059.[Abstract/Free Full Text] 69. Mathias CJ, Fosbraey P, da Costa DF, Thornley A, Bannister R. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure Br Med J (Clin Res Ed) 1986;293:353-354.[CrossRef][Medline] 70. Brignole M, Menozzi C, Moya A, et al. Mechanism of syncope in patients with bundle branch block and negative electrophysiological test Circulation 2001;104:2045-2050.[Abstract/Free Full Text] 71. Menozzi C, Brignole M, Garcia-Civera R, et al. Mechanism of syncope in patients with heart disease and negative electrophysiologic test Circulation 2002;105:2741-2745.[Abstract/Free Full Text] 72. Olshansky B, Poole JE, Johnson G, et al. Syncope predicts the outcome of cardiomyopathy patients: analysis of the SCD-HeFT study J Am Coll Cardiol 2008;51:1277-1282.[Abstract/Free Full Text] 73. Fananapazir L, Epstein ND, Curiel RV, Panza JA, Tripodi D, McAreavey D. Long-term results of dual-chamber (DDD) pacing in obstructive hypertrophic cardiomyopathy Circulation 1994;90:2731-2742.[Abstract/Free Full Text] 74. Shechter A, Stewart WF, Silberstein SD, Lipton RB. Migraine and autonomic nervous system function: a population-based, case-control study Neurology 2002;58:422-427.[Abstract/Free Full Text] 75. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache: report of the quality standards subcommittee of the American Academy of Neurology Neurology 2000;55:754-762.[Free Full Text] 76. Hadjipetrou P, Cox S, Piemonte T, Eisenhauer A. Percutaneous revascularization of atherosclerotic obstruction of aortic arch vessels J Am Coll Cardiol 1999;33:1238-1245.[Abstract/Free Full Text]
Related Article
-
Inside This Issue
J. Am. Coll. Cardiol. 2009 53: A30.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
J. J. C. M. Romme, N. van Dijk, I. K. Go-Schon, J. B. Reitsma, and W. Wieling
Effectiveness of Midodrine treatment in patients with recurrent vasovagal syncope not responding to non-pharmacological treatment (STAND-trial)
Europace,
November 1, 2011;
13(11):
1639 - 1647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Vaddadi, M. D. Esler, T. Dawood, and E. Lambert
Persistence of muscle sympathetic nerve activity during vasovagal syncope
Eur. Heart J.,
August 2, 2010;
31(16):
2027 - 2033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Kapoor
Carotid Sinus Hypersensitivity: A Diagnostic Pearl
J. Am. Coll. Cardiol.,
October 20, 2009;
54(17):
1633 - 1633.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Benditt and J. T. Nguyen
Reply
J. Am. Coll. Cardiol.,
October 20, 2009;
54(17):
1633 - 1634.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Gammage
Impact of syncope on quality of life: do we need another tool?
Europace,
October 1, 2009;
11(10):
1265 - 1266.
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Diagnostic Approach