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INTRODUCTION — Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of an abrupt drop of systemic blood pressure. Reflex syncope (previously termed neutrally-mediated syncope) is TLOC due to a reflex response that encompasses vasodilatation and/or bradycardia (rarely tachycardia), leading to systemic hypotension and cerebral hypoperfusion . Types of reflex syncope include vasovagal syncope, situational syncope, carotid sinus syncope, and some cases without apparent triggers (table 1).
Vasovagal syncope is the most common cause of syncope . Vasovagal syncope may be suggested or diagnosed by a specific history with well-known triggers, but a classic history is not required. Acute vasovagal reactions leading to syncope or presyncope are common also in a number of stressful settings, such as blood donation. The diagnosis can also be suggested by exclusion of other causes of syncope and by a characteristic response to upright tilt table testing during which the patient may become syncopal. In these cases, the syncope is due to hypotension that may be caused by severe bradycardia, vascular dilation (vasodepressor effect), or both. (See "Blood donor screening: Procedures and processes to enhance safety for the blood recipient and the blood donor", section on 'Vasovagal syncope'.)
The treatment of patients with vasovagal syncope and situational syncope will be reviewed here. Discussions of the clinical presentation and diagnostic evaluation of patients with reflex syncope, as well as the pathogenesis, etiology, evaluation and management of syncope in general, are discussed separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and diagnostic evaluation" and "Syncope in adults: Management".)
GENERAL APPROACH TO TREATMENT — No therapy has been proven consistently effective for recurrent vasovagal syncope. However, the following should be considered in all patients with suspected reflex syncope:
●Patients should be reassured about the benign nature of reflex syncope.
●Patients should be educated to avoid potential triggers and identify warning symptoms and, whenever feasible, to lay supine with legs elevated when warning symptoms arise.
●Patients should be instructed on how to perform physical counterpressure maneuvers at the onset of symptoms. (See 'Physical counterpressure maneuvers' below.)
Therapy for patients with reflex syncope is primarily aimed at patients with recurrent reflex syncope. Acute vasovagal reactions are common in a number of stressful settings, such as blood donation. Patients who develop syncope or other symptoms associated with the vasovagal reflex should assume the supine position with legs raised at the onset of such symptoms. (See "Blood donor screening: Procedures and processes to enhance safety for the blood recipient and the blood donor", section on 'Vasovagal syncope'.)
Therapy is particularly important in patients who have recurrent syncope in high-risk settings (eg, commercial vehicle driver, pilot) and who wish to continue these activities. Patients with recurrent episodes may require restriction of activities until therapy is shown to be effective.
Treatment of most forms of situational syncope is based upon avoiding or ameliorating the triggering activity . When the activity cannot be avoided, general treatment measures include maintenance of intravascular volume, protected posture (eg, sitting rather than standing) and slow postural changes. Specific measures may be helpful for certain conditions, such as use of stool softeners in those with defecation syncope, avoidance of excessive fluid intake (especially alcohol) prior to bedtime in post-micturition syncope, and avoidance of large gulps of cold drinks or boluses of food in swallow syncope.
REASSURANCE AND PATIENT EDUCATION — Patients with most forms of reflex syncope should be provided with reassurance and education regarding the nature, risks, and prognosis of the condition (table 2) [1,3].
Patient education involves recognition of the potential symptoms and actions to take upon recognition of any early warning signs as well as identification of potential triggers.
●Patients should be advised to assume the supine position with legs raised at the onset of symptoms, whenever feasible.
●Patients should also be advised to avoid trigger events if possible (eg, prolonged standing, dehydration, cough triggers in "cough syncope," etc) as well as excessive doses of medications that may induce hypotension (eg, vasodilator, diuretics) to the extent that alternative therapies are available.
PHYSICAL COUNTERPRESSURE MANEUVERS — For patients with vasovagal syncope and prodromal symptoms, we recommend physical isometric counterpressure maneuvers such as leg-crossing and/or lower body muscle tensing. These should be initiated upon first recognition of premonitory symptoms (table 2) .
Isometric activity, such as crossing the legs and the arms, may be helpful to offset a syncopal response, but release of this position may be associated with precipitous decline in heart rate and blood pressure. Counter-pressure maneuvers, such as tensing the arms with clenched fists, leg pumping, and leg-crossing, may abort a syncopal episode or at least delay it long enough that patients can assume the supine position . Physical counterpressure maneuvers are intended to reduce lower-extremity venous pooling and therefore improve cardiac output and prevent vasovagal syncope.
Examples of such maneuvers include:
●Leg-crossing with simultaneous tensing of leg, abdominal, and buttock muscles
●Handgrip, which consists of maximum grip on a rubber ball or similar object
●Arm tensing, which involves gripping one hand with the other while simultaneously abducting both arms
The potential efficacy of these maneuvers was evaluated in a randomized trial of 223 patients with recurrent vasovagal syncope and recognizable prodromal symptoms . Patients were randomly assigned to lifestyle modification (eg, avoidance of triggers, increasing fluid and salt intake, lying down at the onset of prodromal symptoms), or lifestyle modification plus physical counterpressure maneuvers. Over a mean follow-up of 14 months, patients assigned to counterpressure maneuvers were significantly less likely to have recurrent syncope compared with those assigned to lifestyle modification alone (32 versus 51 percent).
VOLUME SUPPORT — Usual treatment options include volume expansion by liberalizing salt intake and, occasionally, administration of the mineralocorticoid fludrocortisone (similar to the regimen used in the treatment of orthostatic hypotension). . In some patients, additional measures are needed to prevent symptom recurrences. In such cases, some have recommended support stockings (also called compression stockings). However, these are hard for many patients to put on and they address a part of the body with limited muscle mass and hence limited blood volume. Compression type "bicycling" shorts are easier to use and focus on the major muscle groups in the buttocks and thighs, where large quantities of blood can be sequestered during reflex syncope. The splanchnic bed is another large, highly compliant vascular bed that can sequester large volumes of blood during upright posture and/or reflex syncope. Compressing the splanchnic bed is difficult, but on rare occasions abdominal binders may be attempted. (See "Treatment of orthostatic and postprandial hypotension".)
BETA BLOCKERS — Although beta blockers have been the most commonly used drug therapy for vasovagal syncope, available evidence does not support their efficacy. We agree with the 2009 ESC guidelines that beta blocking drugs are not recommended to treat reflex syncope .
Initial observational data suggested a lower rate of recurrent syncope with beta blocker therapy [6-8]. However, at least four randomized trials have failed to show a benefit, due in part to a large placebo effect [9-12]. Benefit of any therapy is difficult to demonstrate when the placebo effect is so high.
The best data come from the POST trial, which enrolled 208 patients with recurrent syncope and an abnormal tilt table test . The patients were randomly assigned to treatment with placebo or metoprolol, titrated to 200 mg daily, or the highest tolerated dose (average dose 122 mg daily). At one year, the rate of recurrent syncope was 36 percent of both groups, with no benefit in any pre-specified subgroups.
OTHER MEDICATIONS — A variety of medications other than beta blockers have been used in the management of patients with vasovagal syncope. These include midodrine, serotonin reuptake inhibitors, anticholinergics (disopyramide, scopolamine), theophylline, fludrocortisone, desmopressin, and erythropoietin.
●Midodrine, an alpha-1-adrenergic agonist, had a beneficial effect in a small randomized trial and a number of observational studies [13-16]. The benefits have ranged from prevention of syncopal episodes in 95 percent of previously untreated patients  to efficacy for up to 22 months in as many as 78 percent of patients who failed to respond to a beta blocker or other conventional therapy [15,16]. However, the efficacy of midodrine is uncertain, and another alpha agonist, etilefrine, was ineffective in a placebo-controlled study of 126 patients . The ESC 2009 guidelines consider midodrine of uncertain benefit for reflex syncope (in contrast to its utility for orthostatic hypotension) . (See "Treatment of orthostatic and postprandial hypotension".)
●There has been interest in the use of selective serotonin uptake inhibitors, such as sertraline, fluoxetine, or paroxetine [12,18,19]. However, the data are not very convincing. Their presumed effect is at the level of the central nervous system, but it is unclear if it is at the afferent or efferent limb of the reflex arc. The potential clinical efficacy was illustrated in a randomized trial of paroxetine versus placebo in 68 consecutive patients with recurrent syncope and a positive upright tilt test in whom beta blockers, vagolytic agents, and mineralocorticoids were ineffective or poorly tolerated . Paroxetine significantly increased the likelihood of a negative tilt test at one month (62 versus 38 percent) and reduced the rate of spontaneous syncope during follow-up (18 versus 53 percent).
●Disopyramide may be useful due to its negative inotropic (inhibition of myocardial mechanoreceptors) and anticholinergic properties . However, despite apparent benefit in observational studies [20,21], a small controlled trial showed that the rate of recurrent syncope at 29 months was similar with disopyramide and placebo (27 versus 30 percent) . Overall the potential risks of using disopyramide probably outweighs any benefit
●A preliminary report of seven patients refractory to all other medical therapies suggested benefit from methylphenidate . This agent shares some properties with the amphetamines. It is a peripheral vasoconstrictor and stimulates the central nervous system. Again, the evidence is shaky.
●Theophylline  has been tried in small studies with some apparent success. Theophylline may be most effective in patients with a mixed response and associated fatigue during the episodes, although there are no data to support this clinical observation.
ORTHOSTATIC TRAINING PROGRAM — Some patients with vasovagal syncope respond poorly to general measures. Orthostatic or tilt/standing training may be an effective approach, although study results have been mixed [25-30]. Nevertheless, standing train is a reasonable consideration in patients with frequent syncope recurrences.
The efficacy of orthostatic training started in-hospital and continued at home was suggested by a non-randomized study in which 47 patients with recurrent syncope and a positive upright tilt table test who were refractory to traditional therapies were assigned to a tilt-training program or to continued medical therapy, depending upon their consent . The training program included five daily in-hospital upright tilt table studies, increasing in duration from 10 to 50 minutes. The training program was continued at home with the patient instructed to stand against a wall for up to 40 minutes twice a day under supervision of a family member. At a mean follow-up of 18 months, nearly all patients in the training group became tilt-negative (96 versus 26 percent of the control group). None of the trained patients had spontaneous recurrent syncope, compared with 57 percent of controls during 15 to 23 months of follow-up.
However, four randomized controlled studies found that home orthostatic training in patients with syncope and positive tilt table tests did not reduce tilt-positive responses or spontaneous syncopal events [27-30]. In one of these studies, there was a decrease in recurrent syncope with training in the subset of patients with vasodepressor type syncope .
CARDIAC PACEMAKERS — For patients >40 years of age with recurrent syncope with vasovagal bradycardic or asystolic syncopal episodes documented by electrocardiographic monitoring, we suggest permanent cardiac pacing.
Rationale and limitations — Although there is usually a significant bradycardic response in vasovagal syncope, there has been uncertainty about the role of pacemakers because of the severe vasodepressor reactions often found in most episodes of reflex syncope. This is true even for those patients who have asystole during a tilt table test . Only in carotid sinus hypersensitivity is pacing consistently effective. (See "Permanent cardiac pacing: Overview of devices and indications".)
Dual-chamber permanent pacing, especially with rate-drop response, should eliminate most if not all symptoms in patients with a pure cardioinhibitory response. In the patient with a mixed response (significant cardioinhibitory and vasodepressor components), dual-chamber permanent pacing may blunt the symptoms. However, many patients with recurrent vasovagal syncope experience a significant fall in blood pressure prior to any significant decline in heart rate, so pacemakers that sense only changes in heart rate cannot provide pacing in a timely manner .
Evidence on efficacy of pacemakers — Evidence from clinical trials suggests a limited role for pacemaker therapy in patients with vasovagal syncope. Pacemaker therapy is not helpful as a general treatment for all patients with vasovagal syncope, but some evidence suggests that pacemakers may be helpful in selected patients with recurrent syncope who have asystole ≥3 seconds with syncope or asystole ≥6 seconds without syncope.
A 2007 meta-analysis of nine randomized trials (two double blind and seven open label or single blind; total 430 patients) of permanent pacemaker therapy for vasovagal syncope showed no overall benefit from pacemaker implantation and suggested that in the unblinded trials, an "expectation effect" led to an overestimation of the benefits of pacing . Both double blind trials included in the meta-analysis (VPS II and SYNPACE) showed no statistically significant improvement with pacing [34,35].
In contrast, the subsequent double blind ISSUE-3 trial suggested that an implantable loop recorder (ILR) may be helpful in identifying patients with recurrent vasovagal syncope who have asystole and are likely to respond to pacemaker therapy . Among 511 patients aged ≥40 years with ≥3 syncopal episodes within the prior two years, 89 patients were identified with syncope and ≥3 seconds of asystole OR ≥6 seconds of asystole without syncope; of these 89 patients, all 77 received a dual-chamber pacemaker and were randomized to pacemaker programmed ON or OFF. Patients randomized to having the pacemaker programmed ON experienced significantly fewer episodes of recurrent syncope. A possible reason for the difference in results between the ISSUE-3 trial and earlier double-blind trials is that the ISSUE-3 trial used ILR to identify candidates for pacing in contrast to use of tilt testing as a criterion in earlier trials. [1,37,38].
Major society guidelines on pacing — We agree with the published recommendations from the 2008 ACC/AHA/HRS device guidelines and the 2009 ESC guidelines regarding pacing for reflex syncope (table 2) [1,37]:
●Cardiac pacing is reasonable in patients with frequent recurrent reflex syncope, age >40 years, and documented spontaneous cardioinhibitory response during monitoring .
●Permanent pacing may be considered for significantly symptomatic vasovagal syncope associated with bradycardia documented spontaneously or at the time of tilt-table testing .
●Cardiac pacing is not indicated in the absence of a documented cardioinhibitory reflex .
●Permanent pacing is not indicated for situational vasovagal syncope in which avoidance behavior is effective and preferred .
DRIVING RESTRICTIONS FOR PATIENTS WITH VASOVAGAL SYNCOPE — Although vasovagal syncope generally has a benign prognosis, a frequent concern is the potential for injury, particularly during certain activities, such as driving. As the regulations and restrictions on driving differ widely depending upon local law, there is no universal advice that UpToDate can provide regarding one's ability to drive following reflex syncope. Clinicians should become familiar with the pertinent local regulations in this regard [39,40].
In cases where patients are counseled to abstain from driving because of concerns about recurrent syncope, adherence appears to be very low .
Legal requirements for clinicians to report patients with conditions that could impair safe motor vehicle operation vary by state.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Syncope (fainting) (The Basics)")
●Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of an abrupt drop of systemic blood pressure. Reflex syncope (previously termed neutrally-mediated syncope) is TLOC due to a reflex response that encompasses vasodilatation and/or bradycardia (rarely tachycardia), leading to systemic hypotension and cerebral hypoperfusion. Types of reflex syncope include vasovagal syncope, situational syncope, carotid sinus syncope, and some cases without apparent triggers (table 1). (See "Reflex syncope in adults: Clinical presentation and diagnostic evaluation", section on 'Introduction'.)
●No therapy has been proven consistently effective for recurrent vasovagal syncope. However, all patients with suspected reflex syncope should be reassured about the benign nature of reflex syncope, should be educated to avoid potential triggers and identify warning symptoms and, whenever feasible, to perform physical counterpressure maneuvers or lay supine with legs elevated when warning symptoms arise. (See 'General approach to treatment' above.)
●For patients with vasovagal syncope and prodromal symptoms, we recommend physical isometric counterpressure maneuvers such as leg-crossing and/or lower body muscle tensing rather than lying down supine alone (Grade 1B). These should be initiated upon first recognition of premonitory symptoms (table 2). (See 'Physical counterpressure maneuvers' above.)
●For patients >40 years of age with recurrent syncope with vasovagal bradycardic or asystolic syncopal episodes documented by electrocardiographic monitoring, we suggest permanent cardiac pacing. (Grade 2C). (See 'Cardiac pacemakers' above.).
●As the regulations and restrictions on driving differ widely depending upon local law, there is no universal advice that UpToDate can provide regarding one's ability to drive following reflex syncope. Clinicians should become familiar with the pertinent local regulations in this regard. (See 'Driving restrictions for patients with vasovagal syncope' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Brian Olshansky, MD, who contributed to an earlier version of this topic review.
- Task Force for the Diagnosis and Management of Syncope, European Society of Cardiology (ESC), European Heart Rhythm Association (EHRA), et al. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J 2009; 30:2631.
- Chen-Scarabelli C, Scarabelli TM. Neurocardiogenic syncope. BMJ 2004; 329:336.
- Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001; 22:1256.
- 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.
- 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.
- Cox MM, Perlman BA, Mayor MR, et al. Acute and long-term beta-adrenergic blockade for patients with neurocardiogenic syncope. J Am Coll Cardiol 1995; 26:1293.
- Natale A, Sra J, Dhala A, et al. Efficacy of different treatment strategies for neurocardiogenic syncope. Pacing Clin Electrophysiol 1995; 18:655.
- Ventura R, Maas R, Zeidler D, et al. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. Pacing Clin Electrophysiol 2002; 25:816.
- Madrid AH, Ortega J, Rebollo JG, et al. Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study. J Am Coll Cardiol 2001; 37:554.
- Flevari P, Livanis EG, Theodorakis GN, et al. Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients' well-being. J Am Coll Cardiol 2002; 40:499.
- 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.
- Theodorakis GN, Leftheriotis D, Livanis EG, et al. Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study. Europace 2006; 8:193.
- Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998; 79:45.
- Mitro P, Trejbal D, Rybár AR. Midodrine hydrochloride in the treatment of vasovagal syncope. Pacing Clin Electrophysiol 1999; 22:1620.
- Klingenheben T, Credner S, Hohnloser SH. Prospective evaluation of a two-step therapeutic strategy in neurocardiogenic syncope: midodrine as second line treatment in patients refractory to beta-blockers. Pacing Clin Electrophysiol 1999; 22:276.
- Samniah N, Sakaguchi S, Lurie KG, et al. Efficacy and safety of midodrine hydrochloride in patients with refractory vasovagal syncope. Am J Cardiol 2001; 88:A7, 80.
- Raviele A, Brignole M, Sutton R, et al. Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal Syncope International Study. Circulation 1999; 99:1452.
- Di Girolamo E, Di Iorio C, Sabatini P, et al. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 1999; 33:1227.
- Grubb BP, Samoil D, Kosinski D, et al. Use of sertraline hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents. J Am Coll Cardiol 1994; 24:490.
- Milstein S, Buetikofer J, Dunnigan A, et al. Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia. Am J Cardiol 1990; 65:1339.
- Kelly PA, Mann DE, Adler SW, et al. Low dose disopyramide often fails to prevent neurogenic syncope during head-up tilt testing. Pacing Clin Electrophysiol 1994; 17:573.
- Morillo CA, Leitch JW, Yee R, Klein GJ. A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt. J Am Coll Cardiol 1993; 22:1843.
- 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.
- Nelson SD, Stanley M, Love CJ, et al. The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope. Arch Intern Med 1991; 151:2425.
- Di Girolamo E, Di Iorio C, Leonzio L, et al. Usefulness of a tilt training program for the prevention of refractory neurocardiogenic syncope in adolescents: A controlled study. Circulation 1999; 100:1798.
- Reybrouck T, Heidbüchel H, Van de Werf F, Ector H. Tilt training: a treatment for malignant and recurrent neurocardiogenic syncope. Pacing Clin Electrophysiol 2000; 23:493.
- Foglia-Manzillo G, Giada F, Gaggioli G, et al. Efficacy of tilt training in the treatment of neurally mediated syncope. A randomized study. Europace 2004; 6:199.
- On YK, Park J, Huh J, Kim JS. Is home orthostatic self-training effective in preventing neurally mediated syncope? Pacing Clin Electrophysiol 2007; 30:638.
- 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.
- Duygu H, Zoghi M, Turk U, et al. The role of tilt training in preventing recurrent syncope in patients with vasovagal syncope: a prospective and randomized study. Pacing Clin Electrophysiol 2008; 31:592.
- Lacroix D, Kouakam C, Klug D, et al. Asystolic cardiac arrest during head-up tilt test: incidence and therapeutic implications. Pacing Clin Electrophysiol 1997; 20:2746.
- Kosinski DJ, Grubb BP, Wolfe DA. Permanent cardiac pacing as primary therapy for neurocardiogenic (reflex) syncope. Clin Auton Res 2004; 14 Suppl 1:76.
- Sud S, Massel D, Klein GJ, et al. The expectation effect and cardiac pacing for refractory vasovagal syncope. Am J Med 2007; 120:54.
- 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.
- 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.
- Brignole M, Menozzi C, Moya A, et al. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation 2012; 125:2566.
- 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. Circulation 2008; 117:e350.
- Benditt DG. Cardiac pacing for prevention of vasovagal syncope. J Am Coll Cardiol 1999; 33:21.
- Epstein AE, Miles WM, Benditt DG, et al. Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations. A medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology. Circulation 1996; 94:1147.
- Epstein AE, Baessler CA, Curtis AB, et al. Addendum to "Personal and public safety issues related to arrhythmias that may affect consciousness: implications for regulation and physician recommendations: a medical/scientific statement from the American Heart Association and the North American Society of Pacing and Electrophysiology": 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.
- Maas R, Ventura R, Kretzschmar C, et al. Syncope, driving recommendations, and clinical reality: survey of patients. BMJ 2003; 326:21.