Neurocardiogenic syncope
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《英国医生杂志》
1 VA Ann Arbor Healthcare System, Division of Cardiology (111A), 2215 Fuller Road, Ann Arbor, MI 48105, USA, 2 Wayne State University, Detroit, MI 48236, USA
Correspondence to: C Chen-Scarabelli carol.chen-scarabelli@med.va.gov
Introduction
We selected articles from the PubMed database by using the search words "syncope" and "neurocardiogenic syncope." Inclusion criteria were articles published in English, in peer reviewed journals, between 1980 and 2004. Exclusion criteria were articles not published in English, case reports, and articles not published in peer reviewed journals. We incorporated guidelines from the American College of Cardiology, European Society of Cardiology, and American Heart Association, along with a summary of clinical trials. We selected 31 references for this review.
Definition and incidence
Syncope is a symptom, not a disease, and can be classified according to the underlying cause: neurological, metabolic, psychiatric, and cardiac7; cardiac syncope is the most common form. Cardiac syncope includes syncope due to mechanical or structural heart disease, cardiac arrhythmias, and neurocardiogenic syncope (box 1).7
Summary points
Syncope, commonly described as "fainting," is a symptom, not a disease, and can be classified according to the cause, the most common of which is neurocardiogenic syncope
Neurocardiogenic syncope (also known as vasovagal syncope) is a benign condition characterised by a self limited episode of systemic hypotension
Stimulation of the cardiac C fibres results in vasodilation and increased vagal tone, with consequent reduction in cardiac filling and bradycardia, with ensuing syncope
Differential diagnoses include carotid sinus hypersensitivity (resulting from an extreme reflex response to carotid sinus stimulation) and orthostatic hypotension (failure of the autonomic reflex response)
The mainstay of management is education of the patient to avoid situations that predispose to syncope, with anxiety management, coping skills, and reassurance of the patient and others that this is a benign condition
Neurocardiogenic syncope is caused by an abnormal or exaggerated autonomic response to various stimuli, of which the most common are standing and emotion.8 9 The mechanism is poorly understood but involves reflex mediated changes in heart rate or vascular tone, caused by activation of cardiac C fibres.2
Pathophysiology of neurocardiogenic syncope
Although presentation of neurocardiogenic syncope is similar to that of other types of syncope, loss of consciousness in patients with neurocardiogenic syncope may be preceded by prodromata such as nausea, diaphoresis, lightheadedness, blurred vision, headaches, palpitations, paraesthesia, and pallor,3 7 10 11 which usually occur in the upright position (with downward displacement of 300-800 ml of blood3) and resolve almost immediately when the patient assumes the supine position.7 In addition, after recovery, patients with neurocardiogenic syncope may complain of a "washed out" and tired feeling.4 7
Assessment of the symptoms and setting may yield clues as to the possible cause of the syncope. Syncope after cough, defecation, and micturition suggests situational syncope; syncope associated with throat or facial pain (glossopharyngeal or trigeminal neuralgia) is indicative of neurally mediated syncope with neuralgia; and syncope after pain, fear, or noxious stimuli suggests neurocardiogenic syncope.4 Carotid sinus syncope may occur with rotation or turning of the head or pressure on the carotid sinus (for example, carotid massage, shaving, tight collars or neckwear, or tumour compression).4
Box 1: Causes of syncope4 7
Cardiac causes
Structural cardiac or cardiopulmonary disease (aortic stenosis, mitral stenosis, pulmonary stenosis, left atrial myxoma, aortic dissection, acute myocardial infarction, cardiac tamponade, pulmonary embolism, obstructive cardiomyopathy)
Cardiac arrhythmias (tachyarrhythmias, bradyarrhythmias)
Neurally mediated syncopal syndrome (includes neurocardiogenic or vasovagal syncope, carotid sinus syncope, and situational syncope)
Orthostatic (or postural) hypotension
Metabolic causes
Hypoxia
Hypoglycaemia
Hyperventilation
Psychiatric causes
Somatisation disorders
Hysteria
Panic
Fright
Neurological causes
Seizure disorders
Transient ischaemic attacks
Subclavian steal syndrome
Normal pressure hydrocephalus
Diagnosis
Treatment consists of education, manoeuvres to avert syncope, drug treatment, and pacemakers. Education, the mainstay of treatment, includes avoidance of predisposing situations (for example, dehydration, stress, alcohol consumption, extremely warm environments, tight clothing),4 10 anxiety management and coping skills, and reassurance of the patient and others that this is a benign condition. Drug treatments include blockers, agonists, selective serotonin reuptake inhibitors, fludrocortisone, disopyramide, scopolamine, and anticholinergic agents.
Drug treatment
blockers are preferred as initial treatment,10 as they are believed to reduce the degree of mechanoreceptor activation and block the effects of circulating catecholamines.4 However, randomised controlled trials fail to support the efficacy of these drugs, showing no difference from placebo.4 16 17 Furthermore, blockers may worsen syncope through their negative chronotropic effects and atrioventricular node blocking effects.3
agonists work by increasing peripheral vascular resistance and reducing vascular capacitance (to cause increased venous return).3 10 Midodrine, an agonist, has been shown to be effective in several randomised controlled clinical trials.18-20
Selective serotonin reuptake inhibitors selectively block serotonin, which has been shown to induce vagally mediated bradycardia and blood pressure lowering.3 10 Selective serotonin reuptake inhibitors have been used to treat syncope, but their efficacy has been documented in only one randomised controlled trial of 68 patients to date.21 Side effects of these agents include nausea, insomnia, weight gain, and sexual dysfunction.3
Fludrocortisone, a mineralocorticoid that promotes renal reabsorption of sodium to cause increased blood volume,3 10 has been used in the treatment of vasodepressor syncope in both children and adults.22 23 Vascular volume and preload are maintained through the resultant sodium and water retention by fludrocortisone, thereby preventing activation of the cardiac mechanoreceptors.3 However, caution is needed in elderly patients because of the risk of hypertension, cardiac failure, and oedema.24
Disopyramide, a class Ia antiarrhythmic agent with anticholinergic and negative inotropic effects, is not considered first line treatment because of the risk of proarrhythmic and anticholinergic side effects (dry mouth, constipation, blurred vision, and urinary retention).3 Enhanced vagal activity in vasodepressor syncope is counteracted by using anticholinergic agents,10 which are useful when syncope is due solely to increased vagal tone and not to vasodilation.3 Scopolamine, an anticholinergic agent, has central nervous system depressant effects and has been used successfully in some patients with syncope.3
The table summarises clinical trials of various drugs. Most randomised, placebo-controlled clinical studies to date show no differences between the treatment and placebo groups. Other trials that have shown benefit from treatment were not randomised. Most clinical trials, whether randomised or not, had small sample sizes (ranging from 11 to 68 participants) and involved only short term treatment and follow up (most ranging from one week to six months).
Drug treatment in syncope: summary of clinical trials*
Pacemaker treatment
In most people with neurocardiogenic syncope, a fall in blood pressure precedes bradycardia, so pacing may be ineffective in most patients. However, dual chamber pacing may be effective in reducing symptoms if there is a large cardioinhibitory component.14 25 The cardioinhibitory component results from enhanced parasympathetic tone, manifested by slowing of the sinus rate or prolongation of the PR interval and advanced atrioventricular block, either alone or in combination.14 Box 3 lists indications for permanent pacemaker treatment.6 Box 4 outlines a treatment protocol, along with strength of supporting evidence and strength of recommendation.4
Conclusion
American Heart Association. Syncope. www.americanheart.org/presenter.jhtml?identifier=4749 (accessed 30 Jan 2004).
Kapoor WN. Syncope. N Engl J Med 2000;343: 1856-62.
White CM, Tsikouris JP. A review of pathophysiology and therapy of patients with vasovagal syncope. Pharmacotherapy 2000;20: 158-65.
Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al for the Task Force on Syncope, European Society of Cardiology. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001;22: 1256-306.
Kenny RA. Neurally mediated syncope. Clin Geriatr Med 2002;18: 191-210.
Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, et al. ACC expert consensus document: tilt table testing for assessing syncope. J Am Coll Cardiol 1996;28: 263-75.
Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999.
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: 1684-9.
Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, et al. Water ingestion as prophylaxis against syncope. Circulation 2003;108: 2660-5.
Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.
Nair N, Padder FA, Kantharia BK. Pathophysiology and management of neurocardiogenic syncope. Am J Managed Care 2003;9: 327-34.
Sutton R, Petersen ME. The clinical spectrum of neurocardiogenic syncope. J Cardiovasc Electrophysiol 1995;6: 569-76.
Frishman WH, Azer V, Sica D. Drug treatment of orthostatic hypotension and vasovagal syncope. Heart Dis 2003;5: 49-64.
Gregoratos G, Cheitlin M, Conill A, Epstein AE, Fellows C, Ferguson TB Jr, et al. ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: executive summary—a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on pacemaker implantation). Circulation 1998;97: 1325-35.
O'Mahony D. Pathophysiology of carotid sinus hypersensitivity in elderly patients. Lancet 1995;346: 950-2.
Madrid AH, Ortega J, Rebollo JG, Manzano JG, Segovia JG, Sanchez A, 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: 544-9.
Flevari P, Livanis EG, Theodorakis GN, Zarvalis E, Mesiskli T, Kremastinos DT. 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: 499-504.
Kaufmann H, Saadia D, Voustianiouk A. Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study. Ann Neurol 2002;52: 342-5.
Perez-Lugones A, Schweikert R, Parra S, Sra J, Akhtar M, Jaeger F, et al. Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study. J Cardiovasc Electrophysiol 2001;12: 935-8.
Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998;79: 45-9.
DiGirolamo E, Di Iorio C, Sabatini P, Leonzio L, Barbone C, Barsotti A. 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: 1227-30.
Da Costa D, McIntosh S, Kenny RA. Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome. Br Heart J 1993;69: 308-10.
Scott WA, Pongiglione G, Bromberg BI, Schaffer MS, Deal BJ, Fish FA, et al. Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope. Am J Cardiol 1995;76: 400-2.
Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart 1996;76: 507-9.
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.(Carol Chen-Scarabelli, ca)
Correspondence to: C Chen-Scarabelli carol.chen-scarabelli@med.va.gov
Introduction
We selected articles from the PubMed database by using the search words "syncope" and "neurocardiogenic syncope." Inclusion criteria were articles published in English, in peer reviewed journals, between 1980 and 2004. Exclusion criteria were articles not published in English, case reports, and articles not published in peer reviewed journals. We incorporated guidelines from the American College of Cardiology, European Society of Cardiology, and American Heart Association, along with a summary of clinical trials. We selected 31 references for this review.
Definition and incidence
Syncope is a symptom, not a disease, and can be classified according to the underlying cause: neurological, metabolic, psychiatric, and cardiac7; cardiac syncope is the most common form. Cardiac syncope includes syncope due to mechanical or structural heart disease, cardiac arrhythmias, and neurocardiogenic syncope (box 1).7
Summary points
Syncope, commonly described as "fainting," is a symptom, not a disease, and can be classified according to the cause, the most common of which is neurocardiogenic syncope
Neurocardiogenic syncope (also known as vasovagal syncope) is a benign condition characterised by a self limited episode of systemic hypotension
Stimulation of the cardiac C fibres results in vasodilation and increased vagal tone, with consequent reduction in cardiac filling and bradycardia, with ensuing syncope
Differential diagnoses include carotid sinus hypersensitivity (resulting from an extreme reflex response to carotid sinus stimulation) and orthostatic hypotension (failure of the autonomic reflex response)
The mainstay of management is education of the patient to avoid situations that predispose to syncope, with anxiety management, coping skills, and reassurance of the patient and others that this is a benign condition
Neurocardiogenic syncope is caused by an abnormal or exaggerated autonomic response to various stimuli, of which the most common are standing and emotion.8 9 The mechanism is poorly understood but involves reflex mediated changes in heart rate or vascular tone, caused by activation of cardiac C fibres.2
Pathophysiology of neurocardiogenic syncope
Although presentation of neurocardiogenic syncope is similar to that of other types of syncope, loss of consciousness in patients with neurocardiogenic syncope may be preceded by prodromata such as nausea, diaphoresis, lightheadedness, blurred vision, headaches, palpitations, paraesthesia, and pallor,3 7 10 11 which usually occur in the upright position (with downward displacement of 300-800 ml of blood3) and resolve almost immediately when the patient assumes the supine position.7 In addition, after recovery, patients with neurocardiogenic syncope may complain of a "washed out" and tired feeling.4 7
Assessment of the symptoms and setting may yield clues as to the possible cause of the syncope. Syncope after cough, defecation, and micturition suggests situational syncope; syncope associated with throat or facial pain (glossopharyngeal or trigeminal neuralgia) is indicative of neurally mediated syncope with neuralgia; and syncope after pain, fear, or noxious stimuli suggests neurocardiogenic syncope.4 Carotid sinus syncope may occur with rotation or turning of the head or pressure on the carotid sinus (for example, carotid massage, shaving, tight collars or neckwear, or tumour compression).4
Box 1: Causes of syncope4 7
Cardiac causes
Structural cardiac or cardiopulmonary disease (aortic stenosis, mitral stenosis, pulmonary stenosis, left atrial myxoma, aortic dissection, acute myocardial infarction, cardiac tamponade, pulmonary embolism, obstructive cardiomyopathy)
Cardiac arrhythmias (tachyarrhythmias, bradyarrhythmias)
Neurally mediated syncopal syndrome (includes neurocardiogenic or vasovagal syncope, carotid sinus syncope, and situational syncope)
Orthostatic (or postural) hypotension
Metabolic causes
Hypoxia
Hypoglycaemia
Hyperventilation
Psychiatric causes
Somatisation disorders
Hysteria
Panic
Fright
Neurological causes
Seizure disorders
Transient ischaemic attacks
Subclavian steal syndrome
Normal pressure hydrocephalus
Diagnosis
Treatment consists of education, manoeuvres to avert syncope, drug treatment, and pacemakers. Education, the mainstay of treatment, includes avoidance of predisposing situations (for example, dehydration, stress, alcohol consumption, extremely warm environments, tight clothing),4 10 anxiety management and coping skills, and reassurance of the patient and others that this is a benign condition. Drug treatments include blockers, agonists, selective serotonin reuptake inhibitors, fludrocortisone, disopyramide, scopolamine, and anticholinergic agents.
Drug treatment
blockers are preferred as initial treatment,10 as they are believed to reduce the degree of mechanoreceptor activation and block the effects of circulating catecholamines.4 However, randomised controlled trials fail to support the efficacy of these drugs, showing no difference from placebo.4 16 17 Furthermore, blockers may worsen syncope through their negative chronotropic effects and atrioventricular node blocking effects.3
agonists work by increasing peripheral vascular resistance and reducing vascular capacitance (to cause increased venous return).3 10 Midodrine, an agonist, has been shown to be effective in several randomised controlled clinical trials.18-20
Selective serotonin reuptake inhibitors selectively block serotonin, which has been shown to induce vagally mediated bradycardia and blood pressure lowering.3 10 Selective serotonin reuptake inhibitors have been used to treat syncope, but their efficacy has been documented in only one randomised controlled trial of 68 patients to date.21 Side effects of these agents include nausea, insomnia, weight gain, and sexual dysfunction.3
Fludrocortisone, a mineralocorticoid that promotes renal reabsorption of sodium to cause increased blood volume,3 10 has been used in the treatment of vasodepressor syncope in both children and adults.22 23 Vascular volume and preload are maintained through the resultant sodium and water retention by fludrocortisone, thereby preventing activation of the cardiac mechanoreceptors.3 However, caution is needed in elderly patients because of the risk of hypertension, cardiac failure, and oedema.24
Disopyramide, a class Ia antiarrhythmic agent with anticholinergic and negative inotropic effects, is not considered first line treatment because of the risk of proarrhythmic and anticholinergic side effects (dry mouth, constipation, blurred vision, and urinary retention).3 Enhanced vagal activity in vasodepressor syncope is counteracted by using anticholinergic agents,10 which are useful when syncope is due solely to increased vagal tone and not to vasodilation.3 Scopolamine, an anticholinergic agent, has central nervous system depressant effects and has been used successfully in some patients with syncope.3
The table summarises clinical trials of various drugs. Most randomised, placebo-controlled clinical studies to date show no differences between the treatment and placebo groups. Other trials that have shown benefit from treatment were not randomised. Most clinical trials, whether randomised or not, had small sample sizes (ranging from 11 to 68 participants) and involved only short term treatment and follow up (most ranging from one week to six months).
Drug treatment in syncope: summary of clinical trials*
Pacemaker treatment
In most people with neurocardiogenic syncope, a fall in blood pressure precedes bradycardia, so pacing may be ineffective in most patients. However, dual chamber pacing may be effective in reducing symptoms if there is a large cardioinhibitory component.14 25 The cardioinhibitory component results from enhanced parasympathetic tone, manifested by slowing of the sinus rate or prolongation of the PR interval and advanced atrioventricular block, either alone or in combination.14 Box 3 lists indications for permanent pacemaker treatment.6 Box 4 outlines a treatment protocol, along with strength of supporting evidence and strength of recommendation.4
Conclusion
American Heart Association. Syncope. www.americanheart.org/presenter.jhtml?identifier=4749 (accessed 30 Jan 2004).
Kapoor WN. Syncope. N Engl J Med 2000;343: 1856-62.
White CM, Tsikouris JP. A review of pathophysiology and therapy of patients with vasovagal syncope. Pharmacotherapy 2000;20: 158-65.
Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al for the Task Force on Syncope, European Society of Cardiology. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001;22: 1256-306.
Kenny RA. Neurally mediated syncope. Clin Geriatr Med 2002;18: 191-210.
Benditt DG, Ferguson DW, Grubb BP, Kapoor WN, Kugler J, Lerman BB, et al. ACC expert consensus document: tilt table testing for assessing syncope. J Am Coll Cardiol 1996;28: 263-75.
Fogoros RN. Practical cardiac diagnosis: electrophysiologic testing. 3 rd ed. Malden, MA: Blackwell Publishing, 1999.
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: 1684-9.
Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, et al. Water ingestion as prophylaxis against syncope. Circulation 2003;108: 2660-5.
Zaqqa M, Massumi A. Neurally mediated syncope. Tex Heart Institute J 2000;27: 268-72.
Nair N, Padder FA, Kantharia BK. Pathophysiology and management of neurocardiogenic syncope. Am J Managed Care 2003;9: 327-34.
Sutton R, Petersen ME. The clinical spectrum of neurocardiogenic syncope. J Cardiovasc Electrophysiol 1995;6: 569-76.
Frishman WH, Azer V, Sica D. Drug treatment of orthostatic hypotension and vasovagal syncope. Heart Dis 2003;5: 49-64.
Gregoratos G, Cheitlin M, Conill A, Epstein AE, Fellows C, Ferguson TB Jr, et al. ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: executive summary—a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on pacemaker implantation). Circulation 1998;97: 1325-35.
O'Mahony D. Pathophysiology of carotid sinus hypersensitivity in elderly patients. Lancet 1995;346: 950-2.
Madrid AH, Ortega J, Rebollo JG, Manzano JG, Segovia JG, Sanchez A, 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: 544-9.
Flevari P, Livanis EG, Theodorakis GN, Zarvalis E, Mesiskli T, Kremastinos DT. 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: 499-504.
Kaufmann H, Saadia D, Voustianiouk A. Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study. Ann Neurol 2002;52: 342-5.
Perez-Lugones A, Schweikert R, Parra S, Sra J, Akhtar M, Jaeger F, et al. Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study. J Cardiovasc Electrophysiol 2001;12: 935-8.
Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998;79: 45-9.
DiGirolamo E, Di Iorio C, Sabatini P, Leonzio L, Barbone C, Barsotti A. 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: 1227-30.
Da Costa D, McIntosh S, Kenny RA. Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome. Br Heart J 1993;69: 308-10.
Scott WA, Pongiglione G, Bromberg BI, Schaffer MS, Deal BJ, Fish FA, et al. Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope. Am J Cardiol 1995;76: 400-2.
Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart 1996;76: 507-9.
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.(Carol Chen-Scarabelli, ca)