| All of these conditions share the final pathway of withdrawal of sympathetic tone and fall in systemic vascular resistance (SVR). They differ in the origin of the afferent stimulus that triggers the response. Exercise and the postexercise state are unique situations in the discussion of neurocardiogenic syncope, because the physiologic parameters of stroke volume, heart rate, and SVR are different during exercise and rest. Accordingly, tilt table testing, which provides information on the causes of syncope at rest, may not be as applicable to exertional syncope. The complexity of arterial blood pressure control during exercise and the many factors that influence SVR make a single cause of exercise-related syncope unlikely, and a broad-based definition of neurocardiogenic syncope is necessary.
A brief review of arterial blood pressure control and systemic vascular resistance during exercise and rest will help in understanding the possible causes of exercise-related syncope. At rest, 80% of total blood volume is in systemic circulation (extrathoracic), of which about 75% is in the veins and 25% is in the arteries. The remaining 20% of total blood volume is in central circulation (intrathoracic) in the heart, lungs, and intrathoracic veins. Central blood volume can be changed by an increase or loss of total blood volume or by redistribution of systemic blood volume to central blood volume. Shifts of extrathoracic blood to intrathoracic spaces from active venoconstriction of splenic and splanchnic beds, increases in muscle pump activity, and respiratory siphoning caused by deeper respiration can double central blood volume.
Arterial blood pressure is regulated by the autonomic nervous system and its two branches, the parasympathetic and sympathetic chains. Afferent neural signals that are sensitive to stretch emanate from high-pressure baroreceptors (ie, the carotid sinus and aortic arch) and low-pressure cardioreceptors in the atria, ventricles, and pulmonary vessels and terminate in the nucleii tractus solitarii of the medulla oblongata. The nucleii tractus solitarii connects with nearby sympathetic efferent neurons in the rostral ventrolateral nucleus and parasympathetic efferents in the nucleus ambiguus. Together, these areas constitute the vasomotor center of the medulla. Increased stretch in the baroreceptors from increases in systemic blood pressure reduces the sympathetic outflow to the arteries and increases parasympathetic outflow to cardiac conduction tracts. Increased stretch in the cardioreceptors from increases in filling volume inhibits sympathetic outflow and increases parasympathetic activity to cardiac conduction. Unloading the cardioreceptors enhances high-pressure baroreceptor activity, decreases parasympathetic activity, and increases sympathetic outflow signals to the heart and systemic vasculature.
The vasomotor center also receives afferent signaling from supramedullary centers in the amygdala, limbic cortex, and hypothalamus that may override input from baroreceptors. Conscious stimuli such as fright, noxious smells, distressing sights, emotional distress, or rage may invoke different sympathetic and parasympathetic responses in individuals. The common vasovagal faint experienced during these circumstances may be caused by supramedullary afferent stimulation of the nucleus ambiguus parasympathetic fibers and inhibition of the rostral ventrolateral nucleus sympathetic fibers.
Exercise is known to influence the activity of the vasomotor center via afferent input from supramedullary centers. For exercise to progress, vascular resistance must be reduced in exercising skeletal muscle to facilitate increased oxygen delivery. Simultaneously, vascular resistance must increase in nonexercising skeletal muscle to reduce blood flow and preserve cardiac output. In addition, exercise produces higher systemic arterial pressure, which under normal circumstances would be ameliorated by active baroreceptor and cardioreceptor responses. Supramedullary input from higher brain structures has an active role in resetting baroreceptor threshold sensitivity and activity and in selectively regulating SVR in skeletal muscle, thus permitting exercise to progress.
Other influences on circulatory control and SVR include reflex arc inhibition at the local muscle and organ level and hypothalamic-stimulated thermoregulatory input to the vasomotor center. Superficial pain stimulation often invokes a sympathetic response with increased heart rate and SVR. In contrast, deep muscle pain, joint dislocation, testicular injury, and organ distention provoke a parasympathetic response, decrease heart rate and SVR, and produce shock-like symptoms. Heat stress and rising core body temperatures activate hypothalamic thermoregulatory centers that elicit vasodilatory, sympathetic neuromediated increases in dermal blood flow that can reach 5 to 7 L/min of available cardiac output and contribute to loss of central blood volume.
Tilt table testing and the application of lower body negative pressure (LBNP) provide greater understanding of the possible mechanisms involved in syncope during exercise. Thomson et al12 investigated cardioreceptor activity in 30 patients who had recurrent syncope and tilt tests indicating abnormal vasovagal and vasodepressor responses. Using LBNP devices to retard venous return, forearm blood flow was monitored to measure vascular resistance and assess low-pressure cardioreceptor activity. Declining venous return would be expected to decrease cardioreceptor stretch and increase reflex sympathetic tone to SVR, resulting in a decrease of forearm blood flow. In the control subjects, significant decreases in forearm blood flow indicated increased SVR. In the test subjects, forearm resistance did not change or actually decreased. Central venous pressure declines were identical in both groups. The results suggest that cardioreceptor activity in test subjects fails to decline, or, in some cases, is actually stimulated, thus failing to initiate increases in vascular resistance.
In a follow-up study, Thomson et al13 studied the effects of LBNP on venous tone at rest and decreases in splenic volume during exercise. The test group consisted of 25 patients who had known vasovagal syncope, including five who had experienced syncope or near syncope during exercise. Application of LBNP reduced forearm venous volume in control subjects and in all but one test subject, indicating active venoconstriction in response to reductions in venous return. However, when both groups exercised on a stationary bicycle with increases of 25 W every 4 minutes until exhaustion or symptoms developed, test subjects demonstrated no change or increased splenic volume with concordant falls in right atrial pressure. The control subjects demonstrated decreases in splenic volume and no change or increases in right atrial pressure. Two of the five test subjects who reported presyncope or syncope during exercise developed symptoms during the test.
Combined, these two studies suggest that cardioreceptor activity is abnormal in patients with histories of syncope at rest and during exercise. The mechanism involved is failure to elicit increases in sympathetic arterial resistance and increases in splanchnic and splenic venous tone in response to postural or exercise-induced changes in venous return to central circulation. Such patients would be especially at risk for syncope postexercise and during prolonged exercise in hot, humid conditions.
In patients who experience vasovagal syncope with classic presyncopal symptoms of lightheadedness, sweating, and sudden loss of postural tone, tilt table testing has shown abnormal vagal and sympathetic baroreflex activity. With initial onset of tilt, control and tilt-positive patients show increases in blood pressure, pulse, and SVR. As tilt time progresses, arterial pressure declines in tilt-positive patients, followed by drops in SVR and diastolic pressure. Declining heart rate is a relatively later occurrence and ushers in presyncopal symptoms. Frank syncope is initiated by complete withdrawal of sympathetic tone and asystolic pauses. Horizontal positioning restores sympathetic activity, SVR, and heart rate.
Interestingly, syncope is not prevented by prophylactic pacemaker activation, indicating that sympathetic withdrawal and not an overly active para- sympathetic effect on heart rate is the culprit in vasovagal syncope.14 LBNP application has also been used to detect abnormalities in baroreflex sensitivity in patients who have documented histories of syncope.
Using microneurography in peroneal nerves with LBNP, Bechir et al15 published data showing increased sympathetic tone at rest and blunted efferent sympathetic response for induction of increases in SVR. Additional analysis of R-R intervals and pressure correlates used to measure efferent sympathetic activity to cardiac conduction tissue also demonstrated blunted sympathetic outflow in response to LBNP. The conclusion was that patients who have syncope seem to depend more on muscle sympathetic activity to maintain cardiac preload and arterial pressure at rest, and they are less able to increase sympathetic vasoconstrictor outflow in response to orthostasis. Bechir et al used the term "dysfunctional baroreflex activity" to reflect a possible lack of afferent stimuli from the mechanoreceptors and/or baroreceptors, or a dysfunction of the efferent limb to the vascular bed and heart.
Cardioinhibitory reflexes (Bezold-Jarisch) have been implicated as the cause of exercise-induced syncope. Mechanoreceptors in the ventricles (activated by stretch and increased ionotropic force) elicit reflex withdrawal of sympathetic vascular tone and initiate parasympathetic activity to cardiac conduction sites. It has been proposed that, with declining venous return and decreased end diastolic filling pressure, the heart forcibly contracts against an "empty chamber," thus eliciting the cardioinhibitory reflex.16 The latter mechanism may account for the appearance of vasovagal syncope in orthostatic stresses. It remains unclear if this relationship truly exists. Patients who have had cardiac transplants have classic vasovagal syncope even though they have denervated hearts.17,18 Additionally, studies using echocardiography also fail to demonstrate either an empty ventricle or a more vigorous contraction as measured by end-systolic length or fractional systolic shortening during syncopal episodes.19,20 Therefore, vasovagal syncope is not synonymous with the Bezold-Jarisch reflex, nor is cardioinhibitory receptor activation always present in syncopal episodes.
In summary, exercise-related syncope that is not caused by structural or arrythmogenic abnormalities is most likely to be neurocardiogenic in origin. It is likely to recur and has no long-term adverse results. The mechanism of syncope may be related to alterations in afferent cardioreceptor sensitivity and diminished efferent baroreceptor response that, combined, contribute to reduced venous return during exercise and a diminished ability to increase systemic vascular resistance. It is possible that the abrupt withdrawal of SVR elicits a cardioinhibitory reflex that accounts for the profound bradycardia and asystolic pauses that follow, but it is unlikely that cardioinhibitory activity is the sentinel occurrence in syncope. The fact that most athletes do not have exercise-induced syncope raises the question of why some do. Clearly, tilt table testing and LBNP studies are selectively abnormal in patients who have syncope with and without exercise, but they add data to clinical decision making.
Arrhythmic Factors
When an individual begins a bout of exercise, multiple adaptive mechanisms combat the cardiovascular stress. The adrenal glands secrete epinephrine to increase the depolarization rate of the sino-atrial node, which precipitates a tachycardia that helps maintain cardiac output. Cardiac cycle times decrease as well, including the QT interval. In contrast to the cardiac performance enhancement, high sympathetic state can generate a pathologic arrhythmia by direct effect on conduction pathways, ischemia induction, and alteration in sodium-potassium movement across cell membranes. Arrhythmias may also occur in active patients who have acute rupture of atherosclerotic plaques in response to exercise.
In athletes older than 35 and in a significant number of individuals younger than 35, coronary artery disease caused by atherosclerosis is the most common cause of sudden death during exercise.21 Coronary artery disease can induce short-term or prolonged arrhythmias, such as ventricular tachycardia.
Arrhythmogenic right ventricular dysplasia is the most common cause of sudden death in athletes in some parts of the world; however, it seems to be uncommon in the United States.7,22,23 In this disease, myocardial tissue is replaced with fibrofatty tissue that disrupts the normal conducting system of the heart. The stress of exercise may lead to ventricular tachycardia.
Long QT syndrome is a congenital or acquired condition in which the QT segment lengthens after correction for heart rate (figure 1). Many different medications, both prescription and nonprescription, can lead to its development. Each of the seven subtypes of congenital long QT syndrome has characteristic mutations and histories. Of the seven, three are much more prevalent: LQT1, LQT2, and LQT3. LQT1 is most associated with morbidity triggered by exercise, although LQT3 does have an unusual predilection to occur with swimming. Long QT syndrome may lead to torsades de pointes, a life-threatening arrhythmia that may be self-limited or may progress to ventricular fibrillation. Individuals who are predisposed to this arrhythmia have a high likelihood of developing problems with significant exertion.
Polymorphic ventricular tachycardia with normal QT interval is another possible arrhythmic cause of syncope. The incidence of this disorder is unknown, but it may be the cause of 1 in 7 sudden unexplained deaths.24 The disorder tends to be familial, although sporadic cases can occur.
Brugada syndrome is a very uncommon arrhythmic cause of syncope and presyncope in the West but is more common in young Southeast Asian men. This syndrome involves a mutation on the same gene as LQT3. The transport of sodium ions into the cells is affected, but the structure of the heart is not abnormal.
Wolff-Parkinson-White syndrome is an idiopathic or hereditary condition that is characterized by ventricular pre-excitation. Rarely, it progresses to ventricular fibrillation, but it does not usually increase the risk of sudden death. Wolff-Parkinson-White syndrome has been correlated to an increased risk of syncope and presyncope.
Any of these arrhythmias may lead to a syncopal event when exercising. Unfortunately, the warning signs are few, and the result can be serious. Any history of syncope or presyncope with exercise warrants an investigation to exclude these potential causes of arrhythmia.
Structural Factors
Abnormal cardiac structure may not affect function at rest, but with exercise, cardiac output and arterial pressure may be markedly compromised. About 2% to 50% of young individuals who experienced sudden death have abnormal cardiac structure at autopsy.21,23,25 Syncope is a common prodromal symptom of structural heart disease and should be regarded as a sentinel warning sign.
As with cardiac rhythm, exercise modulates cardiac structure. With increased sympathetic activity affecting the heart during exercise, myocardial structure becomes more dynamic with increases in cardiac wall motion and inotropic activity. Cardiomyopathies, fatty infiltration, and scarring from previous bouts of myocarditis or infarction may impair normal myocardial response to exercise.
Arterial anomalies. In the study of sudden death in military recruits by Eckart et al,8 autopsies revealed that the most common coronary artery anomaly found was the left coronary artery arising from the right sinus of Valsalva with a course between the pulmonary artery and aorta. Dynamic cardiac contraction is thought to "pinch off" coronary artery circulation, thus myocardial tissue becomes hypoxic. Anomalous coronary artery is present in 0.3% to 0.8% of the population.26-31
Hypertrophic cardiomyopathy. The most publicized of cardiac abnormalities, hypertrophic cardiomyopathy (HCM), occurs in 1 in 500 people in the general population.27 This genetic condition is the most common cause of sudden death in young athletes, and it should be considered when a first-time exercise-associated syncopal event occurs in an adolescent.26 The abnormal structure of the left ventricle in HCM can lead to lethal arrhythmias, myocardial bridging (ie, compressed tunneled coronary arteries), and ischemia that could result in infarction.27,28 The hypertrophic septum also raises ventricular diastolic pressure with prolongation of ventricular relaxation and an overall decrease in cardiac output.32 Outflow obstruction from an enlarged ventricular septum is worsened with decreased diastolic filling and contracted ventricular cavity dimension. With changes in contractility and cardiac pressures during exercise, symptoms such as presyncope and syncope may develop.
Valve abnormalities. Congenital or acquired structural defects in coronary valves, especially aortic stenosis, can precipitate syncope. In aortic stenosis, outflow obstruction from a noncompliant valve limits cardiac output in response to exercise demand. Increased ventricular pressure may stimulate ventricular stretch receptors and initiate reflex reductions in SVR, thus resulting in a vasodepressor syncopal response.30
Mitral valve prolapse (MVP) can precipitate exertional syncope through multiple mechanisms. Some patients will develop significant mitral regurgitation during exercise, thus increasing their risk of cardiovascular morbidity.31 MVP also seems to precipitate multiple types of arrhythmia leading to syncope. Studies have shown an increased risk of sudden death when MVP is combined with a history of syncope, especially if associated with mitral valve regurgitation.33-35
Initial Management
When an athlete collapses, the ABCs of basic life support (airway, breathing, and circulation) should be immediately assessed. The patient should be moved from any dangerous situation to an appropriate area for triage. Initial resuscitation and evaluation should be done in a head-down, legs-up position. Intravenous fluids should not be administered in most instances, because fluid has not been proven helpful and could actually be harmful if given to a fluid-overloaded patient. If the patient remains unconscious or requires cardiorespiratory support, emergency services should be notified urgently. If the patient regains full consciousness in less than 5 minutes, emergency services are not necessary. Evaluation of the cause can be completed after the patient has stabilized.
Most syncopal episodes have a benign origin. True syncope, by definition, does not require emergency life support procedures. If intervention is necessary, a structural or arrhythmic cause can be suspected and a thorough workup initiated.
Expedient Diagnosis
Timing is extremely important. The history surrounding the event should be carefully evaluated before considering the possible causes. Syncope that occurs immediately after exertion, such as the end of a cross-country race, is most commonly neurocardiogenic syncope. When syncope occurs during exertion, serious concern should be raised for structural and arrhythmic causes.
Age is the second important factor in the diagnosis of exertional syncope. The incidence of atherosclerotic heart disease increases with age and is the most common cause of sudden death in athletes older than 35. Primary consideration of atherosclerosis in older athletes who have exertional presyncope or syncope is paramount.
History. Past syncopal episodes, especially after exertion or after a distressing stimulus, are consistent with neurocardiogenic syncope. Patients should be asked to recall any precipitating events, such as startling noises, full-bladder sensation, colonic cramping, bee sting, or a disturbing visual image such as blood or another person vomiting. If the faint was witnessed, it is important to identify any associated clues to the cause, such as seizure activity or emesis.
At a preparticipation examination, when evaluating an athlete who has a history of syncope, it is vital to get the history from the parent or guardian as well as the athlete. A recent study36 showed that the histories can vary greatly. Medical history, current prescriptions, and over-the-counter medications may provide clues to underlying chronic pathology or other cause in the development of syncope. A family history of sudden death, early cardiac disease, or long QT syndrome should be ascertained. Illicit or performance-enhancing substances, such as cocaine and ephedra, can predispose patients to cardiac disease as well as associated symptoms of chest pain, palpitations, and dyspnea that demand investigation for structural heart problems.
Physical exam. Physical findings often provide some clues to the underlying cause of the collapse. Observation of an obtunded patient may suggest a postictal state or other underlying neurologic or metabolic process. Patients with a cyanotic appearance are most likely experiencing a cardiac or respiratory event. The patient with neurocardiogenic syncope is usually alert and oriented within a few moments of the episode if placed in a head-down, legs-up position. Audible wheezing may be noted. Body habitus, such as a marfanoid stature, may suggest an underlying structural cardiac or aortic abnormality and may also provide information toward a cause. Clubbing may be a sign of pulmonary disorder. Generalized edema or poor skin turgor may be signs of electrolyte disturbance or dehydration. Also, external clues, such as ID bracelets and insulin pumps, may be excellent pointers to the underlying cause.
Vital signs, including body temperature, should be taken with attention to hypotension, bradycardia, tachycardia, and hyperthermia. Orthostatic blood pressures after at least 3 to 5 minutes of standing provide valuable information regarding central blood volume status. Pulse irregularity should be noted. Cardiac examination for changes in heart sounds, murmurs, thrills, and rubs should be performed. Dynamic cardiac auscultation (ie, supine, seated, and standing) may help identify hypertrophic cardiomyopathy. The decrease in venous return with standing or Valsalva's maneuver intensifies the murmur associated with this obstructive malformation.
Special Tests
Any athlete who experiences first-time presyncope or syncope related to exertion should have an electrocardiogram (ECG) before being cleared to return to sport. Conditions such as HCM, prolonged QT interval, heart block, and pre-excitation syndromes such as Wolff-Parkinson-White may have characteristic findings indicating an arrythmogenic or structural cause of the event. If the ECG is normal and the history and examination highly suggest neurocardiogenic syncope, no further testing is needed.37,38 The ECG of a well-trained athlete may have some acceptable abnormal findings, including sinus bradycardia, first- or second-degree AV block, increased voltage of R or S waves, and incomplete right bundle branch block.
If the history and physical exam provide no clues to the cause of the syncope or presyncope, or the event occurred during—as opposed to just after—exertion, further cardiac workup is warranted.1 Likewise, an athlete who has an abnormal exam, abnormal ECG, or history of likely cardiac events, should undergo further diagnostic testing, including echocardiography, maximal exercise testing (preferably in the exercise mode that accompanied the event), Holter or event monitor recordings, and possibly nuclear cardiac imaging, tilt table testing, electrophysiologic studies, and cardiac catheterization.
Echocardiography and stress echocardiography are useful for evaluating valvular abnormalities, ventricular or septal hypertrophy, pulmonary hypertension, and wall motion defects. Technical attention to visualizing the coronary artery architecture should be requested. Maximal exercise stress testing, if possible in the activity that caused the syncope, is also recommended to observe for ischemic changes, provocation of arrythmia, blood pressure response, and exercise capacity.
Controversy exists about the sensitivity and specificity of tilt table testing. While it will often reproduce syncope, tilt table testing has potential for false-positives and false-negatives in athletes, because of baseline increased vagal tone and decreased orthostatic tolerance.37 Event recorders, 24-hour ECG recorders, and implantable loop recorders are useful investigations if the cause of syncope is likely an arrhythmia. Asymptomatic arrhythmia uncovered during recording may not be the cause of syncope. Implantable loop recorders may become the investigation of choice for unexplained syncope, because they seem to yield a diagnosis more often with less cost.39,40 Cardiac catheterization is sometimes needed if ischemia caused by atherosclerosis or myocardial bridging is considered.
If the history or physical exam suggests noncardiac causes, baseline laboratory investigations, including blood sugar and complete blood count, should be considered. Brain natriuretic peptide is a hormone released from the myocardial cells after increased wall stress and increased cardiac volumes. Investigation is underway to see whether this simple lab test could distinguish cardiac versus noncardiac causes of syncope.41
Recommendations for Athletes
Athletes should be encouraged to stay well-hydrated and nourished before training and competition, including maintaining salt intake, especially during hot, humid conditions. Of course, recommending salt intake needs to be tempered against the individual's medical history (ie, salt should not to be recommended to hypertensive patients). Avoiding caffeine can also help maintain hydration and prevent transient arrhythmias.
Numerous medications have been tried to alleviate recurrent benign episodes; beta-blockers are probably the most commonly used. While very successful, their utility for athletes is limited, because they can interfere with athletic performance. Mineralocorticoids,42 alpha1-agonists,43 and selective serotonin reuptake inhibitors44-46 have been prescribed as treatments for neurocardiogenic syncope. Although some of the data are positive, more clinical studies are needed on the effectiveness of medication to treat exercise-induced syncope.
Return-to-Play Issues
The 36th Bethesda Conference guidelines for participation (table 2) are generally accepted as valuable recommendations for return to play.47 Athletes who have a history of neurocardiogenic syncope are typically not restricted from activity. If a structural or arrhythmogenic cause is identified, the athlete must be restricted from play according to the current 36th Bethesda Conference recommendations.47 Further consultation with a cardiologist or cardiothoracic surgeon is recommended.
TABLE 2. Selected Recommendations of the 36th Bethesda Conference That May Relate to Syncope
|
|
| Pathology |
Return-to-Play Recommendation |
| Aortic stenosis |
Mild with no other test abnormalities: no restriction
Moderate: may compete in less intense sports
Severe: total restriction from sports |
Arrythmogenic right ventricular
dysplasia |
Restriction from all but class 1A sports* |
| Brugada syndrome |
Restriction from all but class 1A sports* |
| Coronary artery disease |
In general, athletes who have significant heart disease and who are at substantially increased risk should be restricted to class 1A sports* and avoid intensely competitive situations. See guidelines for specifics. |
Congenital aberrant coronary
artery |
Without surgery: full restriction from sports
With surgery: may participate in sports 3 mo postop if maximal stress test is normal. |
| Hypertrophic cardiomyopathy |
Restriction from all but class 1A sports* |
| Long QT syndrome |
Restriction from all but class 1A sports* in most cases.
Patients who are genotype positive but phenotype negative may play all sports without restriction. |
| Mitral valve prolapse |
Asymptomatic: no restriction from sports
If associated with syncope: restriction fromall but class 1A sports* |
| Myocarditis |
No sports for 6 mo after onset of symptoms. May return to sport if electrocardiogram, echocardiogram, stress testing, and laboratory investigation are normal. |
| Neurocardiogenic syncope |
No restrictions |
Polymorphic ventricular
tachycardia |
Restriction from all but class 1A sports.*
If symptomatic, consider ICD implantation. |
| Wolff-Parkinson-White syndrome |
If associated with syncope, electrophysiological ablation should be considered |
|
|
Heeding Ominous Signs
Exertional syncope is an uncommon occurrence that is most often caused by neurocardiogenic mechanisms. It may, however, be the only symptom of a potentially life-threatening abnormality. Presyncope or syncope occurring during active exercise has a greater likelihood of having structural or arrythmogenic causes and warrants complete cardiac evaluation.
References
- O'Connor FG, Oriscello RG, Levine BD: Exercise-related syncope in the young athlete: reassurance, restriction or referral? Am Fam Physician 1999;60(7):2001-2008
- Mosqueda-Garcia R, Furlan R, Tank J, et al: The elusive pathophysiology of neurally mediated syncope. Circulation 2000;102(23):2898-2906
- Kapoor WN: Syncope. N Engl J Med 2000;343(25):1856-1862
- Savage DD, Corwin L, McGee DL, et al: Epidemiologic features of isolated syncope: the Framingham Study. Stroke 1985;16(4):626-629
- Goldschlager N, Epstein AE, Grubb BP, et al: Etiologic considerations in the patient with syncope and an apparently normal heart. Arch Intern Med 2003;163(2):151-162
- Colivicchi F, Ammirati F, Santini M: Epidemiology and prognostic implications of syncope in young competing athletes. Eur Heart J 2004;25(19):1749-1753
- Corrado D, Basso C, Shiavon M, et al: Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998;339(6):364-369
- Eckart RE, Scoville SL, Campbell CL, et al: Sudden death in young adults: a 25-year review of autopsies in military recruits. Ann Intern Med 2004;141(11):829-834
- Noakes TD: Hyponatremia in distance runners: fluid and sodium balance during exercise. Curr Sports Med Reports 2002;1:197-207
- Hoefnagels WA, Padberg GW, Overweg J, et al: Transient loss of consciousness: the value of the history for distinguishing seizure from syncope. J Neurol 1991;238(1):39-43
- Campagna JA, Carter C: Clinical relevance of the Bezold-Jarisch reflex. Anesthesiology 2003:98(5):1250-1260
- Thomson HL, Wright K, Frenneaux M: Baroreflex sensitivity in patients with vasovagal syncope. Circulation 1997;95(2):395-400
- Thomson HL, Atherton JJ, Khafagi FA, et al: Failure of reflex venoconstriction during exercise in patients with vasovagal syncope. Circulation 1996;93(5):953-959
- 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(17):2224-2229
- Bechir M, Binggeli C, Corti R, et al: Dysfunctional baroreflex regulation of sympathetic nerve activity in patients with vasovagal syncope. Circulation 2003;107(12):1620-1625
- Davrath LR, Gotshall RW, Tucker A, et al: The heart is not necessarily empty at syncope. Aviat Space Environ Med 1999;70(3 pt 1):213-219
- Montebugnoli L, Montanari G: Vasovagal syncope in heart transplant patients during dental surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87(6):666-669
- Scherrer U, Vissing S, Morgan BJ, et al: Vasovagal syncope after infusion of a vasodilator in a heart-transplant recipient. N Engl J Med 1990;322(9):602-604
- Liu JE, Hahn RT, Stein KM, et al: Left ventricular geometry and function preceding neurally mediated syncope. Circulation 2000;101(7):777-783
- Novak V, Honos G, Schondorf R: Is the heart 'empty' at syncope? J Auton Nerv Syst 1996;60(1-2):83-92
- Burke AP, Farb A, Virmani R, et al: Sports-related and non–sports-related sudden cardiac death in young adults. Am Heart J 1991;121(2 pt 1):568-575
- Pelliccia A, Maron BJ: Preparticipation cardiovascular evaluation of the competitive athlete: perspectives from the 30-year Italian experience. Am J Cardiol 1995;75(12):827-829
- Maron BJ: Cardiovascular risks to young persons on the athletic field. Ann Intern Med 1998;129(5):379-386
- Tester DJ, Spoon DB, Valdivia HH, et al: Targeted mutational analysis of the RyR2-encoded cardiac ryanodine receptor in sudden unexplained death: a molecular autopsy of 49 medical examiner/coroner's cases. Mayo Clin Proc 2004;79(11):1380-1384
- Van Camp SP, Bloor CM, Mueller FO, et al: Nontraumatic sports death in high school and college athletes. Med Sci Sports Exerc 1995;27(5):641-647
- Maron BJ, Shirani J, Poliac LC, et al: Sudden death in young competitive athletes: clinical, demographic, and pathological profiles. JAMA 1996;276(3):199-204
- Maron BJ: Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287(10):1308-1320
- Yetman AT, McCrindle BW, MacDonald C, et al: Myocardial bridging in children with hypertrophic cardiomyopathy—a risk factor for sudden death. N Engl J Med 1998;339(17):1201-1209
- Maron BJ: Sudden death in young athletes. N Engl J Med 2003;349(11):1064-1075
- Carabello BA, Crawford FA Jr: Valvular heart disease. N Engl J Med 1997;337(1):32-41. [Published erratum in N Engl J Med 1997; 337(7):507 and 2001; 345(22):1652]
- Stoddard MF, Prince CR, Dillon S, et al: Exercise-induced mitral regurgitation is a predictor of morbid events in subjects with mitral valve prolapse. J Am Coll Cardiol 1995;25(3):693-699
- Nishimura RA, Holmes DR Jr: Clinical practice: hypertrophic obstructive cardiomyopathy. N Engl J Med 2004;350(13):1320-1327 [Published erratum in N Engl J Med 2004;351(10):1038]
- Kligfield P, Levy D, Devereux RB, et al: Arrhythmias and sudden death in mitral valve prolapse. Am Heart J 1987;113(5):1298-1307
- Kligfield P, Devereux RB: Is the mitral valve prolapse patient at high risk of sudden death identifiable? Cardiovasc Clin 1990;21(1):143-157
- Alpert JS: Association between arrhythmias and mitral valve prolapse. Arch Intern Med 1984;144(12):2333-2334
- Carek PJ, Futrell M, Heuston WJ: The prepaticipation physical examination history: who has the correct answers? Clin J Sport Med 1999;9(3):124-128
- Blue JG, Pecci MA: The collapsed athlete. Orth Clin North Am 2002;33(3):471-478
- Grubb BP: Clinical practice: neurocardiogenic syncope. N Engl J Med 2005;352(10):1004-1010
- Krahn AD, Klein GJ, Yee R, et al: Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 2001;104(1):46-51
- Krahn AD, Klein GJ, Skanes AC, et al: Insertable loop recorder use for detection of intermittent arrhythmias. Pacing Clin Electrophysiol 2004;27(5):657-664
- Tanimoto K, Yukiiri K, Mizushige K, et al: Usefulness of brain natriuretic peptide as a marker for separating cardiac and noncardiac causes of syncope. Am J Cardiol 2004;93(2):228-230
- 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(5):400-402
- Ward CR, Gray JC, Gilroy JJ, et al: Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998;79(1):45-49
- 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(2):490-494
- Grubb BP, Wolfe DA, Samoil D, et al: Uselfulness of fluoxetine hydrochloride for prevention of resistant upright tilt induced syncope. Pacing Clin Electrophysiol 1993;16(3 pt 1):458-464
- 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 Cardiol 1999;33(5):1227-1230
- The 36th Bethesda Conference: eligibility recommendations for competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol 2005;45(8)1318-1382. Available at http://www.acc.org/clinical/bethesda//beth36/index.pdf
Dr McAward is a family medicine physician and a primary care sports medicine physician at Memorial Sports Medicine Institute in South Bend, Indiana. Dr Moriarity is a family medicine physician and head team physician at the University of Notre Dame in Notre Dame, Indiana. Address correspondence to Kevin M. McAward, MD, 111 W Jefferson, South Bend, IN 46601; e-mail to kmcaward@memorialsb.org.
Disclosure information: Drs McAward and Moriarity disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.
|
