GENERA LPRINCIPLES

• The evaluation of syncope can be daunting as there are a myriad of circumstances that can cause or mimic this common clinical problem.

• It is a presentation that requires a consistent approach with realization that we often will never know with certainty the original precipitating etiology.

• Our role as consultants is to help risk stratify these patients for future events via diagnostic testing, as appropriate, and to recommend therapy to prevent recurrences and reduce the risk of injury or death.

Def in itio n• The term “syncope” should be applied to situations where there is

Temporary, transient loss of consciousness (TLOC) Complete and, typically, rapid recoveryGlobal cerebral hypoperfusion as the final common pathway regardless of etiology

• Otherwise, the episode should be referred to as “TLOC” so as to include nonsyncopal etiologies in the differential diagnosis (Table 6-1).

Epidemio l o gy• The lifetime incidence of syncope is 30% to 50%.1-3

• It accounts for 3% to 5% of emergency room visits and 1% to 6% of hospital admissions. Many more cases of syncope are not reported.4

• Large population data showed a rate of 6.2 per 1,000 person-years, with an

increasing incidence in the elderly.5 For institutionalized patients over the age of70, the incidence is as high as 23% over 10 years.6

Etio l o gy• Syncope first must be differentiated from nonsyncopal events involving real

or apparent TLOC, such as seizures and falls (Table 6-1).• Further subdivision of true syncope is based on specific

pathophysiologic etiologies that include the following four general categories (Table 6-2) in descending order of frequency:

Neurally mediated (reflex) syncopeOrthostatic syncopePrimary cardiac arrhythmiasStructural cardiac or cardiopulmonary disease

DIA GNO SIS

Cl in ic al Pr esen tatio n• Initial evaluation of syncope utilizes the history, physical examination, and

electrocardiogram (ECG) to classify presumed causes and identify patients who are at high risk for death. There are three key questions that need to be answered with the initial evaluation:

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Is loss of consciousness attributable to syncope or not? Is heart disease present or not?Are there important clinical features in the history that suggest the diagnosis?

• In addition, consideration of inpatient versus outpatient evaluation should depend on comorbidities and initial findings. In general, patients with the following should be admitted to avoid delay and adverse outcomes:

Elderly (age > 65 years) Known structural heart diseaseSymptoms suggestive of primary cardiac syncopeAbnormal ECGSevere orthostatic hypotensionFocal neurological deficits

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Family history of sudden deathExertional syncopeSyncope causing severe injurySyncope while driving

Histo ry• Often, the diagnosis of syncope is evident from the history.• Aspects of the history that need to be explored in order to aid diagnosis

and further categorize the event include a prodrome before the attack, eyewitness accounts during the event, the patient’s recollection immediately after the attack, circumstances that may have played a causative role in the event, and general questions about the patient’s medical history.

• A helpful mnemonic is, “I passed out on the BEACH” (Table 6-3).• For patients with recognizable reflex or orthostatic syncope that

occurs infrequently or as an isolated episode, no further workup is necessary. These patients generally have a good prognosis and can be managed as outpatients with treatments listed below.

• In patients with a suspected cardiac etiology, an inpatient cardiac evaluation is warranted.

Ph ysical Examin atio n• The examination should include assessment of orthostatic vital signs and

careful neurologic, pulmonary, and cardiovascular assessment.Proper orthostatic vital signs include

Blood pressure (BP) checked (both arms) after the patient lies supine for at least 5 minutesBP measured 3 minutes after standingOrthostasis = 20-mmHg decrease in systolic BP and/or 10-mmHg decrease in diastolic BP and/or 10-bpm increase in heart rate (HR)

Cardiovascular findings that may point to cardiogenic syncope include

Arrhythmias (tachyarrhythmias, bradyarrhythmias, and irregularity)Murmurs (especially aortic stenosis or hypertrophic obstructive cardiomyopathy)Evidence for heart failure (S3, S4, edema, and elevated JVD)

Neurologic findings are often absent, but might include evidence of autonomic neuropathy (e.g., inappropriate sweating, lack of HR variability, extreme orthostatic BP changes).

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A firm massage at the carotid artery bifurcation for 5 to 10 seconds may reproduce symptoms, particularly in the elderly.

This maneuver can be performed safely at the bedside with the patient lying recumbent on telemetry monitoring and appropriate bradycardia treatments available.The test is considered positive if it results in a ventricular pause of >3 seconds.Neurologic complications are rare (<0.5%), but the procedure should be avoided in patients with known carotid disease, carotid bruits, or a recent transient ischemic attack (TIA)/cerebrovascular accident.

Diagn o stic Testin g• Given the broad differential, the syncope evaluation is notorious for

triggering extensive, multimodality diagnostic testing.• The 2006 American Heart Association (AHA)/American College of Cardiology

(ACC) algorithm for cardiac evaluation of syncope is outlined in Figure 6-1.7

El ectro cardio graph ySpecific abnormalities to look for on ECG include• Evidence of sinus node dysfunction• Evidence of atrioventricular conduction abnormalities• Tachyarrhythmias (supraventricular tachycardia [SVT], ventricular tachycardia

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[VT], atrial fibrillation [AF])

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• Evidence of ventricular preexcitation (delta waves)• Evidence of underlying structural heart disease

includes Q waves suggestive of prior myocardial infection Wide QRS (>120 milliseconds)Left ventricular hypertrophy pattern suggestive of hypertrophic cardiomyopathy(HCM)Anterior precordial T-wave inversions and/or epsilon waves suggestive of arrhythmogenic right ventricular dysplasia (ARVD)

• Evidence of channelopathy: Long or short QT.Right bundle branch block with down-sloping ST elevation and T-wave inversion in V1–V3 (Brugada pattern).

Imagin g• The expanded cardiac evaluation includes an echocardiogram, exercise

testing, and an ischemic evaluation.In appropriate patients, an exercise stress echo would be sufficient to completeall three aspects of testing (baseline imaging followed by exercise protocol and stress imaging).The echocardiogram alone may be diagnostic in cases of valvular heart disease, cardiomyopathy, or congenital heart disease.Exercise testing is preferable to pharmacologic stress and should be symptom- limited.Noninvasive testing for ischemia should be followed by cardiac catheterization if there is an evidence of ischemia or previously unrecognized infarction.

• Cardiac magnetic resonance imaging or computed tomography may be helpful in

the evaluation of structural heart disease, including HCM, ARVD, or coronary anomalies.

• If an arrhythmic cause is suspected, but not evident on the initial workup or on expanded cardiac evaluation, ambulatory cardiac rhythm monitoring can be achieved via one of the following modalities8:

Holter monitor (24 to 48 hours of continuous recording)Event recorder (1 month of patient-activated or patient-triggered recordings to temporally correlate with symptoms)

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Mobile Continuous Outpatient Telemetry (MCOT) for up to one month of continuous monitoringImplantable loop recorder (years of continuous recording)

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FIGU RE 6- 1 . Al go rith m fo r th e eval uatio n o f syn co pe. (Mo dified fro m American Heart Asso ciatio n /American Co l l ege o fCardio l o gy Fo un datio n . AHA/ACCF scien tific statemen to n th e eval uatio n o f syn co pe. Circul atio n 2006;113:316.)

The choice of monitoring is dependent on the frequency of symptoms and type of suspected arrhythmia. Even in a highly selected population, the diagnostic yield of ambulatory cardiac monitoring is relatively low.

• Tilt table testing has been used traditionally as a diagnostic tool to characterize a patient’s hemodynamic response to controlled postural change from supine to upright state to aid in the diagnosis of a reflex-mediated (neurocardiogenic) syncope.

Physiologically, there is a large volume shift during repositioning, with 500 to

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1000 mL of blood moving from the thorax to the distensible venous system below the diaphragm within the first 10 seconds.

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The hydrostatic pressures created by the upright position result in a similar volume of fluid moving to the interstitial space within 10 minutes.Autonomic vasoconstriction is the key reflex to counter this orthostatic stress, and failure of the vasoconstriction mechanism at any point may result in syncope.An under-filled right ventricle will trigger a strong vagal response, leading to bradycardia and hypotensionResults are classified as primarily vasodepressor, cardioinhibitory, or mixed. Unfortunately, the test has a low sensitivity and reproducibility. It is our institutional bias that a tilt table test adds very little to a thorough history, physical examination, and standard cardiac workup of syncope.

• Electrophysiology studies (EPS) can be useful in selected patients. Indications for EPS include

Abnormal ECG suggesting conduction system causeSyncope during exertion or while supine or in the presence of structural heart diseaseSyncope with associated palpitationsFamily history of sudden deathTo define/ablate identified arrhythmias in patients with high-risk occupations

TREA TMENT

• Treatment of syncope can be broadly defined as preventing recurrences and

reducing the risk of injury or death.• In general, this is tailored to treat the suspected underlying etiology of the syncope.• Various approaches to treating the four etiologies of syncope are shown in Table

6-4.

Medic atio n s• The most common pharmacologic options for preventing venous pooling

and aiding intravascular volume expansion includeMidodrine (2.5 to 10 mg by mouth (PO) three times a day)9,10

Peripheral α-agonist causing both arterial and venous constrictionAdverse effects: paresthesias, piloerection, pruritus, and supine hypertension Avoid in patients with carotid artery disease (CAD), peripheral arterial disease, and acute renal failure

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The only drug shown effective in trials for orthostatic hypotension and reflex- mediated syncope

Fludrocortisone (start 0.1 mg PO daily, can increase by 0.1 mg weekly to

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maximum of 1.0 mg PO daily)Synthetic mineralocorticoid causing sodium retention and volume expansionAdverse effects: hypertension, peripheral edema, and hypokalemia11

An ongoing randomized control trial (POST II) is investigating effectiveness in reflex syncope12

β-Blockers are often prescribed for syncope, though trials do not support thispractice.13

O th er No n ph ar mac o l o gic Th er apies• For reflex syncope, effective treatment may be as simple as avoiding

syncopal precipitants.• When such precipitants cannot be avoided, coping strategies can be helpful.

Isometric muscle contractions can improve venous return and abort frank syncope in patients with a recognizable prodrome.

Lif estyl e/ Risk Mo dif ic atio n• Driving restrictions should be discussed in patients with unexplained

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syncope when appropriate.

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• Recommendations currently vary depending on etiology, underlying disease, type of license held (private versus commercial), and adequacy of treatment.

• If cause of syncope is an active cardiac arrhythmia, patients should be instructed not to drive until successful treatment has been initiated and the patient has received permission from the treating physician.

• In general, in patients with a serious episode of syncope that is not clearly due to a reversible etiology, guidelines recommend driving restriction for 3 to 6 syncope- free months. Also, federal law and variable state law pertinent to licensure in these individuals exist and should be consulted when applicable.

O UTCO ME/ PRO GNO SIS

• One-third of the patients with syncope will have a recurrent event within 3 years.• Select subgroups of patients with noncardiac syncope who have an

excellent prognosis. Young, otherwise healthy individuals with a normal ECG and without identifiable heart disease have essentially no increased risk of death relative to the population at large.

• Reflex syncope is associated with no increase in mortality risk.• Syncope from orthostatic hypotension has an excellent prognosis if the

underlying abnormality is easily identified and treated.• In contrast, syncope with an identifiable cardiac etiology carries a higher risk

of mortality, particularly in patients with advanced heart failure. Mortality approaches 45% at 1 year for patients with syncope and left ventricular (LV) ejection fraction <20%.14

REFERENCES

1. Kenny RA, Bhangu J, King-Kallimanis BL. Epidemiology of syncope/collapse in younger and older Western patient populations. Prog Cardiovasc Dis 2013;55:357-363.

2. Ganzeboom KS, Mairuhu G, Reitsma JB, et al. Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35-60 years. J Cariovasc Electrophysiol 2006;17:1172-1176.

3. Manolis AS, Linzer M, Salem D, Estes NA, 3rd. Syncope: current diagnostic evaluation and management.

Ann Intern Med 1990;112:850-863.4. Shen WK, Decker WW, Smars PA, et al. Syncope Evaluation in the Emergency Department Study (SEEDS):

a multidisciplinary approach to syncope management. Circulation 2004;110: 3636-3645.5. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med

2002;347:878-885.6. Lipsitz LA, Wei JY, Rowe JW. Syncope in an elderly, institutionalised population. prevalence, incidence,

and associated risk. Q J Med 1985;55:45-54.

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7. Strickberger SA, Benson DW, Biaggioni I, et al. AHA/ACCF Scientific Statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation: in collaboration with

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the Heart Rhythm Society: endorsed by the American Autonomic Society. Circulation 2006;113:316-327.8. Subbiah R, Gula LJ, Klein GJ, et al. Syncope: review of monitoring modalities. Curr

Cardiol Rev 2008;4:41-48.9. Low PA, Gilden JL, Freeman R, et al. Efficacy of midodrine vs placebo in neurogenic

orthostatic hypotension.A randomized, double-blind multicenter study. Midodrine Study Group. JAMA 1997;277:1046-1051.

10. Wright RA, Kaufmann HC, Perera R, et al. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology 1998;51:120-124.

11. Chobanian AV, Volicer L, Tifft CP, et al. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. N Engl J Med 1979;301:68-73.

12. Raj SR, Rose S, Ritchie D, et al.; POST II Investigators. The Second Prevention of Syncope Trial (POST II)

—a randomized clinical trial of fludrocortisone for the prevention of neurally mediated syncope: rationale and study design. Am Heart J 2006;151:1186.e11-17.

13. Sheldon R, Connolly S, Rose, et al. POST Investigators. Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. Circulation 2006;113:1164-1170.

14. Middlekauff HR, Stevenson WG, Stevenson LW, et al. Syncope in advanced heart failure: high risk of sudden death regardless of origin of syncope. J Am Coll Cardiol 1993;21:110-116.