Current Trends in the Evaluation of Syncope

John D. Hummel, M.DProfessor of Clinical Internal MedicineDirector of Electrophysiology Research

Ohio State University

DefinitionDefinition• a syndrome in which loss of a syndrome in which loss of

consciousness is: consciousness is: – relatively sudden relatively sudden – temporarytemporary– self-terminatingself-terminating– usually rapid recoveryusually rapid recovery

• due to inadequate cerebral due to inadequate cerebral perfusion perfusion

• most often triggered by a fall in most often triggered by a fall in systemic arterial pressuresystemic arterial pressure

Syncope: High Incidence and Likely to Increase

• 7814 participants followed for an average of 17 years, 822 reported syncope

• Estimated 10-year cumulative incidence of syncope was 6%

• The incidence rates increased with age, with a sharp rise at 70 years

• 22% of the study participants with syncope had a recurrence Soteriades et al. NEJM 2002; 347: 878

SyncopeAnnual U.S. Emergency Dept. VisitsAnnual U.S. Emergency Dept. Visits

• ~40% of the population will have at least one syncopal event in their lifetime1

• 10% of falls by elderly are believed due to syncope2

• Major morbidity reported in 6%1 (e.g., fractures, motor vehicle accident)

• Minor injury reported in 29%1

(e.g., lacerations, bruises)

1Kenny RA, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:23-27.2Kapoor W. Medicine. 1990;69:160-175.

SyncopeQOL Impact

0%

25%

50%

75%

100%

73%1

71%2

60%2

37%2

Anxiety/Depression

Alter DailyActivities

RestrictedDriving

ChangeEmployment

1Linzer M. J Clin Epidemiol, 1991;44:1037-1043.2Linzer M. J Gen Int Med, 1994;9:181-186.

Per

cen

t o

f P

atie

nts

Syncope

• In one-third of participants, a cause for syncope could not be assigned

• Risk of death was increased by 31% among all participants with syncope

• Risk of death was doubled among participants with cardiac syncope

• Neurologic syncope (CVA, TIA, seizure) also associated with three-fold risk of stroke

Soteriades et al. NEJM 2002; 347: 878

2• Drug-Induced• ANS Failure

PrimarySecondary

2• Drug-Induced• ANS Failure

PrimarySecondary

Causes of True SyncopeCauses of True Syncope Causes of True SyncopeCauses of True Syncope

OrthostaticOrthostatic CardiacArrhythmia

CardiacArrhythmia

StructuralCardio-

Pulmonary

StructuralCardio-

Pulmonary

1• VVS• CSS• Situational

CoughPost- micturition

3• Bradycardia

Sinus pause/arrestAV block

• TachycardiaVTSVT

• LongQT Synd

4 • Aortic Stenosis• HCM• Pulmonary

Hypertension• Aortic

Dissection

Neurally-Mediated

Reflex

Neurally-Mediated

Reflex

Unexplained Causes = Approximately 10%Unexplained Causes = Approximately 10%

60%60% 15%15% 10%10% 5%5%

• Determine whether the patient is at increased risk for death. • - patients with underlying heart disease• - myocardial ischemia• - Wolff-Parkinson-White syndrome• - life-threatening genetic diseases (LQTS, Brugada)

• Once excluded, the goal becomes identification of the cause of syncope in an attempt to:

• - improve the quality of the patient’s life • - to prevent injury to the patient or others.

AHA/ACCF Scientific Statement on the Evaluation of SyncopeCirculation, February 2006

Goals

The Initial Evaluation:The Initial Evaluation:4 Key Questions4 Key Questions

The Initial Evaluation:The Initial Evaluation:4 Key Questions4 Key Questions

Did the patient suffer ‘true’ Transient Loss of Consciousness (TLOC)?Did the patient suffer ‘true’ Transient Loss of Consciousness (TLOC)?

Was TLOC due to syncope or some other cause?Was TLOC due to syncope or some other cause?

Is heart disease present?Is heart disease present?

Does the medical history (including observations by witnesses) Does the medical history (including observations by witnesses)

suggest a specific diagnosis?suggest a specific diagnosis?

Task Force members, et al. Eur Heart J 2004 25:2054-2072

Syncope vs. Non-Syncopal Events

Strickberger, S. A. et al. Circulation 2006;113:316-327

Flow chart for the diagnostic approach to the patient with syncope

History and Physical: The Most History and Physical: The Most Valuable Part of the Initial Valuable Part of the Initial

EvaluationEvaluation

Prodome/ResiduaActivity/PosturePalpitationsSeizure ActivityMedicationsPrior EpisodesFamily History: Syncope, Sudden Death, Cardiac Disease

H&P yields a diagnosis prior to confirmatory studies in 45% of patients in 7 population based studies (n=1607)

History:

Physical ExamOrthostatic BPMurmurs, Bruits, Pulses, Differential BP’s

ECGECGAbnormal in 50% of patients. Identifies potential cause in 2-11%

• Pre-excitation

• Conduction Delays

• MI

• LVH/RVH (Hypertrophic CM, Aortic Stenosis, Pulmonary HTN)

• QT Interval (QTc=460) should raise suspicion

• Brugada Abnormalities

• Epsilon Waves (ARVD)

Strickberger, S. A. et al. Circulation 2006;113:316-327

ECG changes in the Brugada syndrome

Long QT syndrome-Triggers

• Swimming- LQT1• Auditory/emotional

trigger- LQT2• Inactivity- LQT3

LQT2LQT2

LQT1

LQT3

Strickberger, S. A. et al. Circulation 2006;113:316-327

Different patterns of QT prolongation in LQTS

Kenigsberg, D. N. et al. Circulation 2007;115:e538-e539

Twelve-lead ECG in normal sinus rhythm with epsilon wave

Kenigsberg, D. N. et al. Circulation 2007;115:e538-e539

High-resolution delayed enhanced magnetic resonance image

Neurally Mediated Syncopal Neurally Mediated Syncopal SyndromesSyndromes

The Most Common Cause of The Most Common Cause of SyncopeSyncope

•Vasodepressor Syndrome (Common Faint)

• Micturition/Cough/Sneeze Syncope

• Carotid Hypersensitivity

Reflex Arcs in Neurally Mediated Reflex Arcs in Neurally Mediated SyncopeSyncope

Upright Posture: 15-20% Decrease in Plasma Volume With Upright Posture: 15-20% Decrease in Plasma Volume With Decrease in C.O.Decrease in C.O.

BaroreceptorsMechanoreceptors

Higher Centers(Cortex)

Cranial NervesV, VII, VIII

GI/GUMechanoreceptors

MedullaryVasodepressor Region

Vagus

Reflex ActivationCentral Sympathetic Outflow

Skeletal Muscle& Resp. Pump

Vasodepressor SyncopeVasodepressor SyncopeClinical Syndrome Characterized By:

1. Settings:- young patients, no SHD- Frightening/stressful situation- hunger, fatigue, dehydration, hot room- standing position, sitting occasional

2. Premonitory Signs:- nausea, blurred vision- warmth, diaphoresis- pallor, yawning

3. Syncopal Event:- white, pale- no injury- may be aborted by becoming supine

4. Recovery:- nausea, diaphoresis- fatigue

Tilt TestTilt Test

1. Supine 5 min, 20 min with I.V. pretest2. Tilt 60-70 degrees3. Passive 20-45 minutes4. Isuprel or SL NTG 400 ug spray in neg

for 15-20 minutes5. Endpoint: Syncope or Full Duration

Complete

Rapid Protocols:1. 10 min baseline, Return to supine

and infuse isuprel with HUTT for 20min after 20-25% increase in HR

2. Clomipramine I.V. 5mg (1mg/min) during the first 5 min of 20 min. TTT (spec.93%, sens. 64-83%

Carotid Sinus Massage

• Classification: Cardioihibitory, VDP, Mixed• Abnormal:

– Ventricular pause > 3 seconds or fall in SBP > 50mmHg with symptoms

• Technique:– Recommend continuous ECG and BP monitoring– Assess VDS response with repeat massage after 1 mg of

atropine– Perform CSM with TTT if negative CSM supine: Only

positive in HUTT in 49%• Complications: Neuro in 0.17-0.45%• Contraindicated: Sig. carotid disease• Treatment: PPM for CI, PPM±VDS meds mixed

68 y/o man with a history of CAD, s/p, IMI, 68 y/o man with a history of CAD, s/p, IMI, EF = 45% Presented with 2 recent EF = 45% Presented with 2 recent

syncopal episodes which occurred while syncopal episodes which occurred while sitting without prodrome. sitting without prodrome.

Holter = NSVTHolter = NSVT EPS=NormalEPS=Normal

Right CSM

Echo, Stress Testing

• History and Physical– Presence of definite structural heart disease– Syncope during exertion or when supine– Syncope preceded by palpitations– Family history of SCA– Malignant Syncope– Hx of CADz

• EKG– Bifasicular block or QRS>120 msec– Mobitz I, second degree AV block (off meds)– Asymptomatic Sinus Brady, pause > 3 sec– Long QT, WPW, Brugada, Neg precordial T’s/epsilon– Q waves

EVM, Loop EPS

EchocardiogramEchocardiogram

• Excellent for detecting associated cardiac disease

- Left atrial myxoma- HOCM- Early cardiomyopathy- Valvular disease- Amyloid- Ischemic heart disease- RV abnormalities (+/-)

• Provides key data affecting prognosis and further evaluation

Exercise Testing

• Should be performed in the patient with unexplained syncope, especially if the episode was exercise related.

• Exercise testing – in patients less than 40 years of age, a drop in blood pressure or

failure of blood pressure to rise with exercise raises the question of hypertrophic obstructive cardiomyopathy or left main coronary artery disease.

– In the elderly patient, it may be a manifestation of autonomic failure.

• Exercise testing also screens for catecholaminergic polymorphic ventricular tachycardia and chronotropic incompetence (failure to achieve 100 bpm or 75% MPHR)

• Exercise testing with a functional study can exclude ischemia as a potential cause of syncope

EPS: Indications for Syncope EPS: Indications for Syncope EvaluationEvaluation

Syncope:

Class I:Structural Heart Dz, Unexplained after initial eval.

Palpitations preceding syncope

Palps, Rapid pulse by medical personnelClass II:

Recurrent Unexplained syncope, nl heart and neg TTT

Palps, Inability to obtain recording

Class III:

Known cause of syncope, EPS will not guide Rx

EPS: Catheter Insertion and EPS: Catheter Insertion and TargetsTargets

After IV ProcainamideAfter IV Procainamide

Induction of SMVT – Rate = Induction of SMVT – Rate = 250bpm, SBP < 60250bpm, SBP < 60

WPW: Atrial Fibrillation, WPW: Atrial Fibrillation, Ventricular FibrillationVentricular Fibrillation

Combined Use of EP and Tilt Combined Use of EP and Tilt Table Testing for SyncopeTable Testing for Syncope

Unexplained Syncope (86pts.)

+EPS, 29 (34%) pts. -EPS, 57 (66%) pts.

Tachyarrhythmia Bradyarrhythmia

VT, 21(73%) pts.

-HUT 23(40%) pts.

+HUT 34(60%) pts.

SVT, 5(18%) pts.

SND, 1(3%) pts.

AV Block, 2(6%) pts.

70% of patients were diagnosed with the combined use of EP and Tilt Testing

Sra et al, 1993Sra et al, 1993

Outcome in pts with Unexplained Syncope and Nondiagnostic EPS

1) the incidence of sudden death is low (<2%)

2) the remission rate of syncope is high (80%)

3) the EPS falsely negative in greater than or equal to 20% of patients who continue to have syncope (AV block, SN dysfunction)

Strickberger, S. A. et al. Circulation 2006;113:316-327

Flow chart for the diagnostic approach to the patient with syncope

Types of External Arrhythmia Monitors

• Electrocardiogram: snapshot in time• Holter monitor : 24 to 48 hours of continuous outpatient electrocardiographic

(ECG) recording – Shortcoming: repeated monitoring if an arrhythmia not occur 24-48 hours– Processing can delay action on malignant arrhythmias

• Event recorder: stores 1 to 2 minutes of ECG as soon as the patient activates– Enables much longer period of monitoring– Misses asymptomatic arrhythmias and some symptomatic arrhythmias when pt fails

to activate• Automatic-trigger loop monitors: Records in continuous loop and

automatically captures certain arrhythmias or can be manually activated during symptoms

– Devices can capture detect several types of arrhythmias. – Typically worn for up to 30 days.

• Real-time cardiac surveillance: continuous outpatient ECG monitoring for periods ranging up to several weeks, if necessary.

– Cardiac activity detected by 3 electrodes attached to a ~2 ounce pager-sized sensor or telephone transmitter

– Continuously analyzes the heart rhythm data. If an arrhythmia detected, the monitor automatically transmits data to a central monitoring station for analysis/action

– Any symptoms recorded by the patient are also transmitted.

Kinlay, S. et. al. Ann Intern Med 1996;124:16-20

Cumulative number of patients who sent an electrocardiogram from an event recorder by the number of days needed to record an electrocardiogram during

palpitations

Prospective, randomized crossover comparison 48 hour holter to 30 day EVM

Twice as many symptomatic recordings from EVM as holter

19% of events recorded on EVM required intervention, none from the holter

MCOT Study

• Multicenter randomized controlled trial • 266 pts with palpitations, presyncope,

syncope and nondiagnostic Holter• Randomized to 30 days of MCOT

(Cardionet) or external loop (Loop Group). • Results

– Clinically significant arrhythmias • 55 (41%) pts in the MCOT Group • 19 (14%) patients in the Loop Group (p< 0.001).

Rothman SA, Laughlin JC, Seltzer J, et al. J Cardiovasc Electrophysiol. 2007;18(3):241-247

RAST studyRandomized Assessment of Syncope Trial

• Results:– Primary strategy: diagnostic yield is 47% vs. 20%– Diagnosis overall: 19 vs. 55% (p=0.0014)

39A. Krahn. Circulation 2001; 104: 46-51

ISSUE Study Implications

• HUT outcome was not predictive of vasodepressor vs. cardioinhibitory response– Bradycardia is common in spontaneous VVS -

independent of HUT outcome• Bradycardia is more prevalent in spontaneous

events vs. HUT induced VVS

• Clinical Implication: Consider a strategy of ILR guided evaluation in positive TTT patients unresponsive to medication

Moya A. Circulation. 2001; 104:1261-1267

ISSUE 2Syncopal Episodes per Patient per Year

0.83

0.07 0.05

Non-Specific Therapy

ILR-Based (all patients receiving

antiarrhythmic therapyor pacemaker therapy)

Pacemaker Therapy

Only

Brignole M. Eur Heart J. 2006;27:1085-1092 (ISSUE 2).

Methods:

• A 92% relative reduction in syncope burden and 80% relative reduction in one-year recurrence rate with pacing and antiarrhythmic therapies guided by ILR findings

• 392 patients with suspected neurally-mediated syncope were enrolled

• 103 pts. had an ECG documented syncope, leading to therapy and a follow-up observational period

Results:

Diagnostic Methods & Yield

Test/Procedure Yieldbased on mean time to diagnosis of 5.1

months7

History and Physical (including carotid sinus massage)

49-85% 1, 2

ECG 2-11% 2

Electrophysiology Study without SHD* 11% 3

Electrophysiology Study with SHD 49% 3

Tilt Table Test (without SHD) 11-87% 4, 5

Ambulatory ECG Monitors:

- Holter 2% 7

- External Loop Recorder (2-3 weeks duration) 20% 7

-Insertable Loop Recorder (up to 18 months duration)

65-88% 6, 7

Neurological † (Head CT Scan, Carotid Doppler) 0-4% 4,5,8,9,10

* Structural Heart Disease† MRI not studied

1 Kapoor, et al N Eng J Med, 1983.2 Kapoor, Am J Med, 1991.3 Linzer, et al. Ann Int. Med, 1997.4 Kapoor, Medicine, 1990.5 Kapoor, JAMA, 1992

6 Krahn, Circulation, 19957 Krahn, Cardiology Clinics, 1997.8 Eagle K,, et al. The Yale J Biol and Medicine. 1983; 56: 1-8.9 Day S, et al. Am J Med. 1982; 73: 15-23.10 Stetson P, et al. PACE. 1999; 22 (part II): 782.

Symptom-Rhythm Correlation

Auto Activation Point

Patient Activation Point

Syncope Diagnosis: Role of an ILR

A. Strickberger et al. Circulation 2006; 113: 316-327

AHA/ACC Scientific Statement on the Evaluation of Syncope:

“This approach (ILRs) is

more likely to identify

the mechanism of

syncope than is a

conventional approach

that uses Holter or

event monitors and EP

testing and is cost-

effective.”

Ideal System for Long Term Cardiac Monitoring

• Subcutaneous placement, simple and fast to implant, excellent safety profile.

• Reliably provides information that can aid selection and titration of therapies– High sensitivity detector in ILR– Signal processing software to remove false positives and extract

information at monitoring center– Human over-read at service center to assure information delivered

to physician is clinically relevant

• Simple for the patient – requires little or no compliance– Long-range telemetry for automated data transfer

• Simple for the physician – maximizes practice efficiency, follow up requires minimal work load– Data download tailored to institution/practice

Sub-Q ILR’s: Evolution

Reveal DX2007

Reveal XT, Sleuth ATConfirm2009

Reveal1998

Reveal Plus2000

Automatic detection added

Longevity and ECG memory increased (to 3 yrs., 49.5

minutes), with episode logs, ICD sensing technology, MRI

labeling, and remote monitoring added

AF detection and long-term trended diagnostics (the Cardiac

Compass and AF Summary Reports) added

Reveal is developed to help diagnose unexplained

syncope

Transoma: the first wireless and automated monitoring system

TransomaSleuth

Transoma‘Sleuth AT”

Medtronic‘Reveal XT’

St. Jude‘Confirm’

Asystole Any single pause >3.0 sec. >1.5, >3.0, >4.5 sec >1.5, >3.0, >4.5 sec

Bradycardia Detection Settings

30, 40, 50 bpm 30, 40, 60 bpm 30, 40, 50 bpm

Tachycardia Detection Settings

120 to 220 bpm, Off 4/4, 6/8, 8/8, 16/16, 32/32 beats

VT = 250 to 520 ms

(115 to 240 bpm)

FVT = 240 to 400 ms

(150 to 250 bpm)

VT = 250 to 520 ms

(115 to 240 bpm)

FVT = 240 to 400 ms

(150 to 250 bpm

AF Detection 20 sec. ECG strips sent to Monitoring Center every 7.5 min.Analysis of ECG data and arrhythmia classification, by Certified Cardiac Techs at Monitoring Center

On board detection algorithm based on R to R variability

On board detection algorithm based on R to R variability but can’t turn on until clinical study is completed and approved by FDA for AF detection

Memory for ECG Data

673 min. between automatic, wireless transmission to the Monitoring Center

ILR: 43 min.

PDM: 630 min.

49.5 minutes total between scheduled office visits

Memory available on ILR only

Download to Carelink

48 minutes total between scheduled office visits

Memory available on ILR only

Download to TTM

ILR Battery Life 18 to 30 months 36 months 36months

Competing ILR’s

RUP Study: Importance of Wireless Download

1.Franco Giada et al.. J Am Coll Cardiol 2007;49:1951–6

Automatic detection mode in the REVEAL was activated, but no significant arrhythmias were recorded: because ILR memory “was always saturated by inappropriate activations.”

Krahn et al, PACE 2004; 27: 657

Loss of tissue contact from shape/form factor

Importance of an Antenna

Medicomp Arrhythmia Access

Patient Activated Report Page

Arrhythmia Access-Sleuth Patient Summary Report

The Value of Advanced Diagnostics

• Daily AF burden

• V-rate during AF

• Avg. day/night HR

• Patient activity

• Heart rate variability (HRV)

Note: All clinic, physician, and patient names and data in this document are fictitious

Value of Advanced Diagnostics

How long do the episodes last?

When did the episodes start?

What is the AF burden?

Note: All clinic, physician, and patient names and data in this document are fictitious

Summary: Current Trends in Arrhythmia Monitoring

• Greater use of external continuous auto-trigger wireless loop recorders

• Greater Use of Implantable Loop Recorders:– Diagnosis of Syncope– Management of Atrial Fibrillation– Evaluation of Cyptogenic Stroke

Reference

• AHA/ACCF Scientific Statement on the Evaluation of Syncope: From the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascualr 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 the Heart Rhythm Society. S. Adam Strickberger, et al. JACC. 2006; 47; 473-484

Other References

• Soteriades et al. NEJM 2002; 347: 878• Rothman SA, et al. J Cardiovasc

Electrophysiol. 2007;18(3):241-247• Franco Giada et al.. J Am Coll Cardiol

2007;49:1951–6• A. Krahn, et. Al. Circulation 2001; 104: 46-

51• Moya A, et Al. Circulation. 2001; 104:1261-

1267• Brignole M., et. AL. Eur Heart J.

2006;27:1085-1092

ACC/AHA Guidelines for Pacing With Syncope

• Class I– Third degree AV block with or without Sx’s– Advanced 2nd deg. AV block – Documented sinus brady causing syncope– Sustained Pause dependent VT eliminated by pacing– CSM causing syncope, pauses > 3 seconds min CSM in absence of culprit meds

• Class II– Sinus brady less than 40 bpm or pauses > 3 seconds awake without symptoms– Abnormal Sinus node function on EPS– Neuromuscular diseases (Kearns-Sayre, Erb’s dystrophy, Peroneal Muscular Atrophy) with any

degree AV block (including first degree)– Bifasicular, Trifasicular block (other causes excluded)– SVT resolved only by ATP (RFA and meds failed or not elected)– High risk congenital LQTS patients– Prevention of recurrent drug refractory AF in pts with coexisting SN disease– ASx CSM with > 3 second pause– Significantly symptomatic, recurrent VDS associated with bradycardia– Brady-Tachy syndrome requiring therapy

• Class III– Reversible Causes (drug toxicity, Lyme, non-essential drug Rx causative)– Documentation of syncope in absence of bradycardia– Situational syncope with bradycardia when avoidance effective

ACC/AHA Guidelines for Pacing With Syncope

• Class I– Third degree AV block with or without Sx’s– Advanced 2nd deg. AV block – Documented sinus brady causing syncope– Sustained Pause dependent VT

eliminated by pacing– CSM causing syncope, pauses > 3

seconds CSM in absence of culprit meds with sx’s

ACC/AHA Guidelines for Pacing With Syncope

• Class II– Sinus brady less than 40 bpm or pauses > 3 seconds awake

without symptoms– Abnormal Sinus node function on EPS– Neuromuscular diseases (Kearns-Sayre, Myotonic dystrophy,

Peroneal Muscular Atrophy) with any degree AV block (including first degree)

– Bifasicular, Trifasicular block (other causes excluded)– SVT resolved only by ATP (RFA and meds failed or not elected)– High risk congenital LQTS patients– Prevention of recurrent drug refractory AF in pts with coexisting

SN disease– ASx CSM with > 3 second pause– Significantly symptomatic, recurrent VDS associated with

bradycardia– Brady-Tachy syndrome requiring therapy

ACC/AHA Guidelines for Pacing With Syncope

• Class III– Reversible Causes (drug toxicity, Lyme,

non-essential drug Rx causative)– Documentation of syncope in absence of

bradycardia– Situational syncope with bradycardia

when avoidance effective