SYNCOPE Mechanisms and Management

John Telles MD, FACC August 9, 2006

Case Study

20 y/o female competitive cyclistDizzy when stands up quicklySyncope during training ride

Syncope (Greek to interrupt)Syncope is the sudden transient loss of consciousness and postural tone with spontaneous recovery.Loss of consciousness occurs within 10 seconds of hypoperfusion of the reticular activating system in the mid brain.

Maintenance of Postural Normaltension

Upright posture results in translocation of 30% of central blood volume to dependent body parts within seconds and transcapillary fluid shifts over 30 minutes further reduce blood volume by 5%.Compensatory responses Muscle pump Nuerovascular compensation Humoral compensation Local vascular

Bergan J et al. N Engl J Med 2006;355:488-498Action of the Musculovenous Pump in Lowering Venous Pressure in the Leg

Maintenance of Postural NormaltensionNeurovascular Compensation

High pressure mechanoreceptors

Low pressure mechanoreceptors

Syncope is important because.It is commonCostlyMay be disablingMay be only warning sign before sudden death

Relative Frequency of Syncope15% of children before the age of 1816% during 10 year period in men aged 40- 5919% during 10 year period in women aged 40 4923% during 10 year period in elderly > 70 years oldRecurrence in 35% in 3 years

Syncope MortalityLow mortality vs. high mortality

Neurally-mediated syncope vs. syncope with a cardiac cause

Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-885. [Framingham Study Population]

Syncope: Key questions to address with initial evaluationIs the loss of consciousness attributable to syncope or not?

Is heart disease present or absent?

Are there important clinical features in the history that suggest the diagnosis?

Syncope MimicsDisorders without impairment of consciousnessFalls Drop attacksCataplexyPsychogenic pseudo-syncopeTransient ischemic attacksDisorders with loss of consciousnessMetabolic disordersEpilepsyIntoxicationsVertebrobasilar transient ischemic attacks

Differential Diagnosis of Syncope: Seizures vs Hypotension

Causes of True SyncopeOrthostaticCardiacArrhythmiaStructuralCardio-Pulmonary1VVSCSSSituationalCoughPost- Micturition

2Drug-Induced ANS FailurePrimarySecondary3BradySN DysfunctionAV BlockTachyVTSVTLong QT Syndrome4 Acute Myocardial IschemiaAortic StenosisHCMPulmonary HypertensionAortic Dissection

Neurally-MediatedUnexplained Causes = Approximately 1/3DG Benditt, MD. U of M Cardiac Arrhythmia Center

Causes of Syncope1Soteriades ES, et al. NEJM. 2002;347:878-885. 2 Linzer M, et al. Ann Intern Med. 1997;126:989-996.

Framingham Cohort1 (N=727)Composite Data (Linzer2) (N=1,002) CausePrevalence Mean %CausePrevalence Mean %Vasovagal21Vasovagal18Orthostatic9.3Orthostatic8Cardiac10Cardiac18Seizure5.2Neurologic10Medication6.8Medication3Stroke/TIA4.2Situational5Other7.8Carotid Sinus1Unknown35.9Unknown34

Causes of Syncope by AgeYounger PatientVasovagalSituationalPsychiatricLong QT*Brugada syndrome*WPW syndrome*RV dysplasia*Hypertrophic cardiomyopathy*Catecholaminergic VTOther genetic syndromesOlder PatientCardiac**MechanicalArrhythmicOrthostatic hypotensionDrug-inducedNeurally mediatedMultifactorialUnderlined: benign * Rare, not benign ** Not benign.

Syncope: Key questions to address with initial evaluationIs the loss of consciousness attributable to syncope or not?

Is heart disease present or absent?

Are there important clinical features in the history that suggest the diagnosis?

Syncope: Important Historical FeaturesQuestions about circumstances just prior to attackPosition (supine, sitting , standing)Activity (rest, change in posture, during or immediately after exercise, during or immediately after urination, defecation or swallowing)Predisposing factors (crowded or warm place, prolonged standing post-prandial period) and of precipitating events (fear, intense pain, neck movements)

Questions about onset of the attackNausea, vomiting, feeling cold, sweating, pain in chest, pain in neck, or shoulders,

Syncope: Important Historical FeaturesQuestions about onset of the attackNausea, vomiting, feeling cold, sweating, pain in chest, pain in neck, or shoulders,

Syncope: Important Historical FeaturesQuestions about attack (eye witness)Skin color (pallor, cyanotic)Duration of loss of consciousnessMovements ( tonic-clonic, etc.)Tongue biting

Questions about the end of the attackNausea, vomiting, diaphoresis, feeling cold, muscle aches, confusion, skin color, wounds

Syncope: Important Historical FeatureQuestions about backgroundNumber and duration of syncope spellsFamily history of arrhythmic disease or sudden deathPresence of cardiac diseaseNeurological disease (Parkinsons, epilepsy, narcolepsy)Internal history (Diabetes)Medications (Hypotensive, negative chronotropic and antidepressant agents)

Clinical Features Suggesting Specific Cause of SyncopeNeurally-Mediated SyncopeAbsence of cardiac diseaseLong history of syncopeAfter sudden unexpected, unpleasant sensationProlonged standing in crowded, hot placesNausea vomiting associated with syncopeDuring or after a mealWith head rotation or pressure on carotid sinusAfter exertion

Clinical Features Suggesting Specific Cause of SyncopeSyncope due to orthostatic hypotensionAfter standing upTemporal relationship to taking a medication that can cause hypotensionProlonged standingPresence of autonomic neuropathyAfter exertion

Clinical Features Suggestion Cause of SyncopeCardiac SyncopePresence of structural heart diseaseWith exertion or supinePreceded by palpitationsFamily history of sudden death

Initial Exam: Thorough PhysicalVital signsHeart rateOrthostatic blood pressure change

Cardiovascular exam: Is heart disease present? ECG: Long QT, pre-excitation, conduction system diseaseEcho: LV function, valve status, HCM

Neurological exam

Carotid sinus massage Perform under clinically appropriate conditions preferably during head-up tilt testMonitor both ECG and BP

Carotid Sinus Massage (CSM)Method1Massage, 5-10 secondsDont occludeSupine and upright posture (on tilt table)Outcome3 second asystole and/or 50 mmHg fall in systolic BP with reproduction of symptoms = Carotid Sinus SyndromeAbsolute contraindications2Carotid bruit, known significant carotid arterial disease, previous CVA, MI last 3 months Complications Primarily neurologicalLess than 0.2%3Usually transient

Syncope: Diagnostic Testing in Hospital Strongly RecommendedSuspected/known significant heart diseaseECG abnormalities suggesting potential life-threatening arrhythmic causeSyncope during exerciseSevere injury or accidentFamily history of premature sudden death

Diagnostic Methods and Yields

**Structural Heart Disease

ProcedureHistory and Physical ExamYield*25-35%1ECG2-11%2MonitoringHolter Monitoring2%3

External Loop Recorder20% 3Insertable Loop Recorder43-88%4,5,6Test/ProcedureTilt Table11-87% 1,7EP Study without SHD**11% 8EP Study with SHD49% 1

Heart Monitoring OptionsILREvent Recorders (non-lead and loop)Holter Monitor12-Lead2 Days7-30 DaysUp to 14 Months10 SecondsOPTIONTIME (Months) 01234567891011121314

Insertable Loop Recorder (ILR)The ILR is an implantable patient and automatically activated monitoring system that records subcutaneous ECG and is indicated for:

Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias

Patients who experience transient symptoms that may suggest a cardiac arrhythmia

Symptom-Rhythm Correlation with the ILRCASE: 65 year-old man with syncope accompanied by brief retrograde amnesia.Medtronic data on file.CASE: 56 year-old woman with refractory syncope accompanied with seizures.

Head-Up Tilt Test (HUT)Protocols vary

Useful as diagnostic adjunct in atypical syncope cases

Useful in teaching patients to recognize prodromal symptoms

Not useful in assessing treatment

Response to Tilt Table Testing Normal Vasal vagal

Response to Tilt Table Testing POTS Dysautonomia

Indication for Tilt Table TestingThe evaluation of recurrent syncope, or a single syncopal event accompanied by physical injury, motor vehicle accident, or in high risk setting in which clinical features suggest vasovagal

In patients in whom dysautonomias may contribute to symptomatic hypotension

Evaluation of recurrent exercise induced syncope in patients without structural heart disease

Conventional EP Testing in SyncopeGreater diagnostic value in older patients or those with SHD

Less diagnostic value in healthy patients without SHD

Useful diagnostic observations:Inducible monomorphic VTSNRT > 3000 ms or CSNRT > 600 msInducible SVT with hypotensionHV interval 100 ms (especially in absence of inducible VT)Pacing induced infra-nodal block

Diagnostic Limitations of EPSDifficult to correlate spontaneous events and laboratory findings

Positive findings1Without SHD: 6-17%With SHD: 25-71%

Less effective in assessing bradyarrhythmias than tachyarrhythmias2

EPS findings must be consistent with clinical historyBeware of false positive

cardiac syncope can be a harbinger of sudden death.Survival with and without syncope6-month mortality rate of greater than 10%Cardiac syncope doubled the risk of deathIncludes cardiac arrhythmias and SHD

Soteriades ES, et al. N Engl J Med. 2002;347:878.

Syncope Due to Cardiac ArrhythmiasBradyarrhythmiasSinus arrest, exit blockHigh grade or acute complete AV blockCan be accompanied by vasodilatation (VVS, CSS)

TachyarrhythmiasAtrial fibrillation/flutter with rapid ventricular rate (eg, pre-excitation syndrome)Paroxysmal SVT or VTTorsade de pointes

Syncope Due to Structural Cardiovascular Disease: Principle MechanismsAcute MI/Ischemia2 neural reflex bradycardiaVasodilatation, arrhythmias, low output (rare)Hypertrophic cardiomyopathyLimited output during exertion (increased obstruction, greater demand), arrhythmias, neural reflexAcute aortic dissectionNeural reflex mechanism, pericardial tamponadePulmonary embolus/ pulmonary hypertensionNeural reflex, inadequate flow with exertionValvular abnormalitiesAortic stenosis Limited output, neural reflex dilation in peripheryMitral stenosis, atrial myxoma Obstruction to adequate flow

Neurally-Mediated Reflex SyncopeVasovagal Syncope (VVS)Carotid Sinus Syndrome (CSS)Situational syncopePost-micturitionCoughSwallow DefecationBlood drawing, etc..

VVS Clinical PathophysiologyNeurally-mediated physiologic reflex mechanism with two components:1. Cardioinhibitory ( HR) 2. Vasodepressor ( BP) despite heart beats, no significant BP generatedBoth components are usually present

12

VVS IncidenceMost common form of syncope8% to 37% (mean 18%) of syncope cases

Depends on population sampledYoung without SHD, incidenceOlder with SHD, incidence

VVS General Treatment Measures Optimal treatment strategies for VVS are a source of debateTreatment goalsAcute interventionPhysical maneuvers, eg, crossing legs or tugging armsLowering headLying down

Long-term preventionTilt trainingEducationDiet, fluids, salt Support hoseDrug therapyPacing

CSSCarotid Sinus SyndromeSyncope clearly associated with carotid sinus stimulation is rare (1% of syncope)

CSS may be an important cause of unexplained syncope/falls in older individuals

Prevalence higher than previously believed

Carotid Sinus Hypersensitivity (CSH)No symptomsNo treatment

CSSEtiologySensory nerve endings in the carotid sinus walls respond to deformationPrevious neck surgery may contributeIncreased afferent signals to brain stemReflex increase in efferent vagal activity and diminution of sympathetic tone results in bradycardia and vasodilatation

Carotid Sinus

SAFE PACESyncope And Falls in the Elderly Pacing And Carotid Sinus EvaluationObjectiveDetermine whether cardiac pacing reduces falls in older adults with carotid sinus hypersensitivityRandomized controlled trial (N=175)Adults > 50 years, non-accidental fall, positive CSMPacing (n=87) vs. No Pacing (n=88)ResultsMore than 1/3 of adults over 50 years presented to the Emergency Department because of a falls have CS hypersensitivityWith pacing, falls 70%Syncopal events 53%Injurious events 70%Kenny RA. J Am Coll Cardiol. 2001;38:1491-1496.

Orthostatic HypotensionEtiologyDrug-induced (very common)DiureticsVasodilatorsPrimary autonomic failureMultiple system atrophyParkinsons DiseasePostural Orthostatic Tachycardia Syndrome (POTS)Secondary autonomic failureDiabetes Alcohol Amyloid

Treatment Strategies for Orthostatic IntolerancePatient education, injury avoidanceHydrationFluids, salt, diet Minimize caffeine/alcoholSleeping with head of bed elevatedTilt training, leg crossing, arm pullSupport hoseDrug therapiesFludrocortisone, midodrine, erythropoietinTachy-Pacing (probably not useful)

Syncope and DrivingI want to die peacefully in my sleep like my grandfather did, not like the screaming passengers in his car. George Burns

Syncope and Driving: Medical-Legal ConcernsState of California requires physicians to report, in good faith, patients who have a physical or mental condition which, in the physicians judgment, impairs the patients ability to exercise reasonable and ordinary control over a motor vehicle. The report may be made without the patients informed consent.The physician is obliged to inform the patient of the severity of the condition and that operating a motor vehicle is advised against. This informed advise should be documented in the medical record.

Syncope and Driving: Medical Legal ConcernsExamples of syncopal conditions that would prohibit driving

Untreated syncope in patients with heart disease

Undiagnosed recurrent syncope which occurs without prodrome and can occur while sitting

20 y/o female cyclist, dizzy when stands quickly, syncope during training ride

20 y/o female cyclist, dizzy when stands quickly, snycope during training ride

Sitting: HR 65, BP 120/80 , Standing: HR 90, BP 115/80

EKG normal

20 y/o female cyclist, dizzy with standing quickly, syncope on training ride

Sitting: HR 65, BP 120/80 Standing: HR 90, BP 115/80

EKG normal

Echo normal

20 y/o female cyclist, dizzy when stands quickly, syncope during training rideSitting:HR 65, BP 120/80, Standing HR 90, BP 115/80EKG normalEcho normalExercise test normal

20 y/o female cyclist Dizzy when stands quickly, syncope during training rideSitting: HR 65, BP 120/80, Standing: HR 90 BP 115/80EKG normalEcho normalExercise test normalTilt test abnormal

Diagnosis Postural orthostatic tachycardia syndrome POTSTreatment hydration fludrocortisone midodrine welbutrin zoloft procrit atacand @ HS

Diagnostic ObjectivesDistinguish true syncope from syncope mimicsDetermine presence of heart disease and risk for sudden deathEstablish the cause of syncope with sufficient certainty to:Assess prognosis confidentlyInitiate effective preventive treatment

How to Evaluate Syncope*EPS if BBB or LVEF < 40%

History: Patient and witnessesPhysical: Including carotid massage and ECGTransient orreversible cause?Suspected cardiac or arrhythmic cause?Neurocardiogenic cause?No obvious cause?No heart disease?No work-up or chronic therapy1st episode?Tilt tableLoop recorderAdmit, cardiology consult, EPS*-Rx++++yesyesyesRxRxRxNo Rxyesno-Olshansky B. Syncope: Mechanisms and Management. Futura Pub. Co. 1998.Referral-

The physiology of syncope is depicted graphically in this slide. The afferent trigger signals (eg, pain, emotional upset, dehydration) are not depicted. In the efferent loop of the neural reflex:

Parasympathetic signals from the cerebral cortex reduce heart rate and slow (or block) AV conduction.Decreased sympathetic activity results in vasodilatation.Bradycardia and/or hypotension occur.Carotid baroreceptors and other mechanoreceptors provide paradoxical feedback to the central nervous system, aggravating bradycardia and vasodilatation.

The result may be a downward spiral in heart rate and blood pressure leading to syncope.

Benditt DG, Lurie KG, Adler SW, et al. Pathophysiology of vasovagal syncope. In: Neurally mediated syncope: Pathophysiology, investigations and treatment. Blanc JJ, Benditt D, Sutton R. Bakken Research Center Series, v. 10. Armonk, NY: Futura, 1996.

This slide provides a simple classification of the principal causes of syncope, listed from the most commonly observed (left) to the least common (right). This ranking may be helpful in thinking about the strategy for evaluating syncope in individual patients.Within the boxes, the most common causes of syncope are indicated for each of the major diagnostic groups. The terms neurally-mediated syncope, neurally-mediated reflex syncope, and neurocardiogenic syncope are generally used synonymously. For purposes of this presentation, neurally-mediated syncope is used to define a broad category; neurocardiogenic or vasovagal syncope refer to a specific condition.VVSVasovagal SyncopeCSSCarotid Sinus SyndromeANSAutonomic Nervous SystemHCMHypertrophic Cardiomyopathy

DG Benditt, MD. University of Minnesota Cardiac Arrhythmia CenterThere are many causes of syncopetoo many to list in this presentationand new and creative ways to pass out are always possible.The table on the left provides data on the incidence and prognosis of syncope from the Framingham study. The right shows composite data from five studies. Vasovagal, in any study, represents the most common cause for syncope. This is also referred to as neurocardiogenic syncope. But there are a variety of dysautonomic syndromes that can lead to syncope.The term vasovagal syncope, sometimes referred to as neurocardiogenic syncope, encompasses many conditions initiated by an abrupt change in blood pressure and heart rate, heart rate alone, blood pressure alone, or associated with other dysautonomic conditions that lead to the neurocardiogenic reflex. The episode can be situationalwitnessing a needle stickor due to an underlying conditioncarotid hypersensitivity, for example.Cardiovascular causes for syncope include those due to organic heart disease such as aortic stenosis or hypertrophic cardiomyopathy, or due to arrhythmias such as ventricular tachycardia and ventricular fibrillation.About one-third of patients will never have a cause diagnosed,1,2 and in some studies this number is as much as 50%.3 In these patients, the most likely cause for syncope is benign and is most likely due to a neurocardiogenic reflex. 1 Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-885.2 Linzer M, Yang E, Estes N, et al. Diagnosing syncope. Ann Intern Med. 1997;126(12):989-996.3Kapoor W. Evaluation and outcome of patients with syncope. Medicine. 1990;69:160-175.

All diagnoses are presumptive unless an episode is observed with documentation of heart rate, blood pressure, cerebral blood flow, EEG activity, etc.Diagnoses can be categorized by the age of the patient. For patients younger than the age of 40 to 50, there are several benign causes for syndrome. One must, however, be aware of congenital syndromes, such as long QT interval syndrome, Brugada syndrome, WPW syndrome, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and others as possible causes for syncope. For the older patient, cardiac causes for syncope are common and must be considered seriously. In addition, orthostatic hypotension, while it is benign, can be difficult to treat. Drug-induced causes for syncope include vasodilators, beta blockers, and drugs that lower blood pressure and cause vasodilation in the older patient. This combined with a less robust autonomic nervous system can lead to difficulties with abrupt changes in position and stress. Indeed, many older patients have multifactorial causes for syncope.

Olshansky B. Syncope: Overview and approach to management. In: Grubb B and Olshansky B. eds. Syncope: Mechanisms and Management. Armonk, NY:Futura Pub Co. 1998:15-71.

HCMHypertrophic Cardiomyopathy

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Carotid sinus massage (CSM) is an often overlooked, yet highly cost effective test, especially in older syncope patients. CSM must be applied with care, and the method described here1 has proven both safe and effective. Note that an abnormal response to CSM (i.e., Carotid Sinus Hypersensitivity, CSH) is not diagnostic of Carotid Sinus Syndrome (CSS). Reproduction of symptoms is a crucial diagnostic element. To achieve symptom reproduction, it may be useful to conduct CSM with the patient in the upright posture. If the latter is to be done, the patient should be safely secured to a tilt table in order to prevent injury from a fall.

1Kenny RA, OShea D, Parry SW. The Newcastle protocols for head-up tilt table testing in the diagnosis of vasovagal syncope, carotid sinus hypersensitivity, and related disorders. Heart. 2000;83:564-569. 2Linzer M, Yang EH, Estes M, et al. Diagnosing Syncope: Part 1: Value of history, physical examination, and electrocardiography. Ann Intern Med. 1997;126(12):989-996.3Munro N, McIntosh S, Lawson J, et al. Incidence of complications after carotid sinus massage in older patients with syncope. J Am Geriatr Soc. 1994;42:1248-1251.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Current testing modalities are limited in terms of ability to capture infrequent events, patient compliance, and diagnostic yield.9 Diagnostic yield is defined as the number of patients with diagnostically positive test results, divided by the number of patients tested. Or, in the case of monitoring studies, the sum of true-positive and true-negative test results divided by the number of patients tested (Linzer M, et al. Ann Intern Med. 1997;126(12):989-996). Due to the complex diagnosis of syncope, patients may undergo extensive investigations which are often low-yield, expensive, and/or invasive.1 And when inconclusive, these tests are often repeated.9These are the more typical diagnostic tests. 1Kapoor W. Medicine. 1990;69(3):160-175.2Kapoor W. Am J Med. 1991;90:91-106.3Krahn AD, Klein GJ, Yee R. Cardiol Clin.1997;15(2):313-326.4Krahn AD, Klein GJ, Yee R, Norris C. Am J Cardiol. 1998;82:117-119. 5Krahn AD, Klein GJ, Yee R, et al. Circulation. 1999;99:406-410.6Krahn AD, Klein GJ, Yee R, et al. JACC. 2003;42:495-501.7Kapoor W. JAMA. 1992;268:2553-2560.8Linzer M, Yang B, Estes M, et al. Ann Intern Med. 1997;127:76-86.9Olshansky, B. Syncope: Overview and approach to management. In: Olshansky B and Grubb B, eds. Syncope: Mechanisms and Management. Armonk, NY: Futura Publishing Co;1998:15-71.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.These are examples of ECG recordings obtained by the Reveal ILR system in two symptomatic patients. The gold standard for determining if a syncope episode may be due to an arrhythmia is to record the rhythm during symptoms, i.e., symptom-rhythm correlation. The ILR may help rule-in or rule-out arrhythmogenic causes.These strips depict findings from an ILR interrogation as they appear on the programmer screen. In order to view the event in greater detail, one taps the screen over the ECG of interest. On-screen calipers are available at every zoom level to measure cycle length in milliseconds or beats per minute.Note that the A represents an auto-activated event; the P indicates when the patient activated the device.Left strip: Infra-Hisian AV block: dual chamber pacemaker.Right strip: VT and VF: ICD, meds.

Medtronic data on file.

The rationale for undertaking tilt table testing in patients suspected of having vasovagal (VVS) syncope is summarized here. The test may provide useful diagnostic information and also an opportunity for patients to become more familiar with the condition and its possible warning signs.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Conventional EP testing (i.e., electrical stimulation without autonomic studies such as HUT) has not been highly effective in substantiating a basis for syncope. In this regard, EPS has been more effective in patients with structural cardiovascular disease than in those with normal cardiovascular status. The most important findings at EPS in regard to the evaluation of syncope patients are listed in this slide.

SHDStructural Heart DiseaseSNRTSinus Node Recovery TimeCSNRTCorrected Sinus Node Recovery Time

Benditt D. Syncope. In: Topol E, ed. Textbook of Cardiovascular Medicine. Philadelphia, PA: Lippencott Williams & Wilkins;2002:1529-1542.Lu F and Bergfeldt L. Role of electrophysiologic testing in the syncope evaluation. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.*SHDStructural Heart Disease

1Linzer M, Yang E, Estes M, et al. Diagnosing Syncope. Part 2: Unexplained Syncope. Ann Int Med. 1997;127:76-86.2Lu F and Bergfeldt L. Role of electrophysiologic testing in the syncope evaluation. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.Cardiac causes include both arrhythmias and structural heart problems, both of which contribute to high mortality rates. One of the goals, therefore, is to attempt to either rule out or rule in arrhythmic disorders.The statistic of a 1-year mortality rate ranging from 18-33% was validated in the September 19th, 2002 issue of the New England Journal of Medicine. The incidence and prognosis of syncope was studied in more than 7,800 participants in the Framingham Heart Study from 1971 to 1998. The study found a 6-month mortality rate of greater than 10%.1Cardiac syncope doubled the risk of death .1Syncope of unknown cause was the largest category of causes.250% of syncope cases could not be diagnosed after conventional evaluation of detailed history, physical exam, and ECG.3Because the precise cause of syncope is identified in fewer than half the patients during initial evaluation, the challenge lies in identifying those at high risk for death. Cardiac syncope is not benign.

1 Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-885.2 Kapoor WN. Evaluation and outcome of patients with syncope. Medicine. 1990;69:160-175.3 Linzer M, Yang E, Estes N, et al. Diagnosing syncope. Ann Intern Med. 1997;126(12):989-996.Both excessively slow as well as excessively rapid heart rates may result in sufficient drop in systemic pressure to cause syncope. In the case of tachycardias, the syncope tends to occur at the onset of the episode, before vascular constriction has an opportunity to occur. Syncope may also occur at termination of tachyarrhythmias, if a prolonged pause occurs prior to resumption of a stable rhythm.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.This slide lists important structural cardiovascular abnormalities to be considered during the diagnostic evaluation of syncope.Obstruction of blood flow and arrhythmias are often the mechanisms for the syncope; all are high risk.The list is not intended to be exhaustive of the possibilities, but provides some of the more commonly found conditions.

MImyocardial infarctionHCMhypertrophic cardiomyopathy

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.The neurally-mediated reflex causes of syncope are a group of related conditions in terms of symptomatic hypotension being caused by a variable combination of bradycardia and vasodilatation.

Vasovagal syncope and carotid sinus syndrome are the most frequent conditions in this group. The others occur occasionally and are usually recognized only if a detailed medical history is obtained.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Vasovagal syncope, as in other forms of neurally-mediated reflex syncope, is due to systemic hypotension resulting in a transient period of inadequate cerebral blood flow.

Hypotension is the result of two pathophysiologic components: Marked bradycardia or inappropriately slow heart rate for the blood pressure (i.e., cardioinhibitory feature) Vasodilatation

The relative contribution of these two components varies among patients.

Wieling W, Gert van Dijk J, van Lieshout J, Benditt D. Pathophysiology and clinical presentation. In: Benditt D, Blanc J-J, et al. eds. The Evaluation and Treatment of Syncope. Elmsford, NY: Futura. 2003;11-22.

The incidence of vasovagal syncope is poorly known.The published data that exists mostly dates from before the advent of tilt table testing.Linzer surveyed the literature and found published prevalences varying from 8% to 37% (mean 18%) of cases of syncope.Standards for diagnosis and reporting are still emerging.

Linzer MD, Yang EH, Estes M, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Ann Intern Med. 1997;126(12):989-996.Optimal management strategies for VVS are a source of debate. Long-term prevention measures include:Patient education, reassurance, and instruction. Control of fluids, salt, and diet may help reduce incidence.Support hose may limit blood pooling in the legs and feet.Drug therapy should be used as a second line option. Midodrine and beta-adrenergic blockers are the agents most thoroughly studied to datePacing may benefit some patients. Subsequent slides will examine the utility of pacing in very symptomatic VVS patients.

When the patient has a relatively long prodrome, evasive action may prevent injury if not syncope. This might include physical maneuvers such as crossing the legs, lowering the head, or lying down.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Carotid sinus syndrome (CSS) is an important and often overlooked cause of syncope, and in addition is believed to be a frequent cause of unexplained falls in older individuals. The underlying cause of CSS is considered to be a hypersensitive carotid sinus. Carotid Sinus Hypersensitivity (CSH) is diagnosed by using Carotid Sinus Massage (CSM). The method of carotid sinus massage, and the findings diagnostic of CSS were presented on previous slides.

Kenny RA, Richardson D, Steen N, et al. Carotid sinus syndrome: A modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). J Am Coll Cardiol. 2001;38:1491-1496.Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Sutton R. Carotid sinus syndrome: clinical presentation, epidemiology, and natural history. In: Neurally Mediated Syncope: Pathophysiology, Investigation and Treatment. Blanc JJ, Benditt D, Sutton R. eds. Armonk, NY: Futura;1996:138.The etiology of CSS rests in part from afferent signals arising in the carotid baroreceptors, and inappropriate concomitant signals from nearby neck muscles.

Sensory nerve endings in the carotid sinus walls respond to deformation.An increase in afferent traffic results in cardioinhibition and vasodilatation.Deafferentation of nearby neck muscles may contribute. The CNS is not informed of neck movement and consequently the carotid baroreceptor afferents are interpreted as indicating a rise in central arterial pressure.

Blanc JJ, LHeveder J, Mansourati J, et al. Pathophysiology of carotid sinus syndrome. In: Neurally mediated syncope: Pathophysiology, investigation and treatment. Blanc JJ, Benditt D, Sutton R. eds. Armonk, NY: Futura;1996:25-29.Kenny RA, McIntosh SJ. Carotid sinus syndrome. In: Syncope in the Older Patient. Kenny RA ed. London: Chapman & Hall Medical; 1996:107-108.

The study was a randomized controlled trial, pacing versus no pacing, performed at the Royal Victoria Infirmary in Newcastle, between April 1998 and May 2000. Patients were followed for 12 months after randomization.The inclusion criteria were consecutive adults, over the age of 50 years, presenting with a non-accidental fall, who exhibited a positive response to CSM and who had no evidence of cognitive impairment or dementia.In patients with unexplained falls and a diagnosis of cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the total number of falls by 70%, total syncopal events by 53%, and total injurious events by 70%.There was a statistically significant reduction in the total number of falls among the pacemaker patient group, with a 70% reduction in total falls compared with the control group.Only 28 patients reported syncope; 22 syncopal events were reported by paced patients and 47 by controls. Although there was a 50% reduction in the overall number of syncopal episodes, this did not reach statistical significance.There was also a 70% reduction in the total number of injury events, from 202 in the control group to 61 in paced patients.

Kenny RA, Richardson D, Steen N, et al. Carotid sinus syndrome: A modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). J Am Coll Cardiol. 2001;38:1491-1496.

Orthostatic hypotension is an important cause of syncope. The medical history is usually sufficient to establish the diagnosis. However, defining the specific cause requires careful consideration of a number of important conditions.The most important conditions predisposing to orthostatic syncope are listed here.

Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncopeUpdate 2004. Europace. 2004;6:467-537.There is a valid approach to assessing patients with syncope. The most crucial aspect is to obtain a careful history from the patient, family, and witnesses. Based on the history and physical exam, a plan can be developed. There may be a transient or reversible cause for syncope and the problem can be easily solved with no further work-up or chronic therapy. If there is a suspected cardiac cause for syncope or an arrhythmic cause for syncope, hospital admission must be considered as well as an electrophysiology consult. An electrophysiologic study may be useful in the patient with a bundle branch block or a moderately impaired ejection fraction. For neurocardiogenic syncope, if it is clear that this is the potential etiology with no obvious trigger and no heart disease, no admission is required. If it is the first episode, no therapy is required. If recurrent episodes occur without obvious trigger, a tilt table test might be useful. Further, in patients with recurrent syncope, an external loop recorder is useful and should be considered before a tilt table test if palpitations are associated with syncope. If a diagnosis cannot be made in or out of the hospital, then an implantable loop recorder may be useful to help make the diagnosis. Olshansky, B. Syncope: Overview and approach to management. In: Olshansky B and Grubb B, eds. Syncope: Mechanisms and Management. Armonk, NY: Futura Publishing Co;1998:15-71.