Syncope A Diagnostic and Treatment Strategy David G. Benditt, M.D. University of Minnesota Medical School Minneapolis, MN USA Richard Sutton, DScMed Royal

SyncopeA Diagnostic and

Treatment Strategy

David G. Benditt, M.D.University of Minnesota Medical School

Minneapolis, MN USA

Richard Sutton, DScMedRoyal Brompton Hospital

London, UK

Transient Loss of Consciousness (TLOC)

Classification of Transient Loss of Consciousness (TLOC)

Syncope

• Neurally-mediated reflex syndromes

• Orthostatic hypotension

• Cardiac arrhythmias

• Structural cardiovascular disease

Disorders Mimicking Syncope

• With loss of consciousness, i.e., seizure disorders, concussion

• Without loss of consciousness, i.e., psychogenic “pseudo-syncope”

Real or Apparent TLOCReal or Apparent TLOC

Brignole M, et al. Europace, 2004;6:467-537.

Syncope – A Symptom, Not a Diagnosis

Self-limited loss of consciousness and postural tone

Relatively rapid onset

Variable warning symptoms

Spontaneous, complete, and usually prompt recovery without medical or surgical intervention

Underlying mechanism is transient global cerebral hypoperfusion.

Underlying mechanism is transient global cerebral hypoperfusion.


Presentation Overview

I. Etiology, Prevalence, Impact

II. Diagnosis

III. Specific Conditions and Treatment

IV. Special Issues

Section I:

Etiology, Prevalence, Impact

Causes of True Syncope

OrthostaticOrthostatic CardiacArrhythmia

CardiacArrhythmia

StructuralCardio-

Pulmonary

StructuralCardio-

Pulmonary

1• VVS• CSS• Situational

CoughPost- Micturition

2• Drug-Induced• ANS Failure

PrimarySecondary

3• Brady

SN Dysfunction

AV Block

• TachyVTSVT

• Long QT Syndrome

4 • Acute

Myocardial Ischemia

• Aortic Stenosis

• HCM• Pulmonary

Hypertension• Aortic

Dissection

Neurally-Mediated

Neurally-Mediated

Unexplained Causes = Approximately 1/3Unexplained Causes = Approximately 1/3

DG Benditt, MD. U of M Cardiac Arrhythmia Center

Syncope Mimics

Acute intoxication (e.g., alcohol)

Seizures

Sleep disorders

Somatization disorder (psychogenic pseudo-syncope)

Trauma/concussion

Hypoglycemia

Hyperventilation


Impact of Syncope

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

3Brignole M, et al. Europace. 2003;5:293-298.4 Blanc J-J, et al. Eur Heart J. 2002;23:815-820.5Campbell A, et al. Age and Ageing. 1981;10:264-270.

40% will experience syncope at least once in a lifetime1

1-6% of hospital admissions2

1% of emergency room visits per year3,4

10% of falls by elderly are due to syncope5

Major morbidity reported in 6%1

eg, fractures, motor vehicle accidents

Minor injury in 29%1

eg, lacerations, bruises

Impact of Syncope: US Trends

300

320

340

360

380

400

420

440

'96 '97 '98 '99 '00 '01 '02

*All patients discharged with syncope and collapse (ICD-9 Code:780.2) listed among diagnoses.NHDS 2003. NAMCS 2002.

Inpatient Trend* Physician Office Visits**

**Syncope and collapse (ICD-9 Code: 780.2) listed as primary reason for visit.

400

500

600

700

800

900

1,000

1,100

1,200

'96 '97 '98 '99 '00 '01

(000s) (000s)

30

40

50

60

70

80

'96 '97 '98 '99 '00 '01 '02

Impact of Syncope: US Trends

500

600

700

800

900

'96 '97 '98 '99 '00 '01 '02

EmergencyDepartment Visits*

HospitalOutpatient Visits*

(000s)

+ Not available

NHAMCS 2002.

+

*Syncope and collapse (ICD-9 Code:780.2) listed as primary reason for visit.

(000s)

Impact of Syncope: NHS Hospitals, England, 2002-2003*

74,813 hospital consults for syncope and collapse

80% required hospital admission

Average length of stay: 6.1 days

327,201 hospital bed days, second only to senility

*Hospital Episode Statistics, Dept. of Health, Eng. 2002-2003.

Impact of Syncope: Costs

Estimated hospital costs exceeded $10 billion US1

Estimated physician office expenses exceeded $470 million2

£104,285 spent on 1,334 patients with syncopal codes (UK) (EaSyAS)3

• Hospital admission: 67% of investigational costs

Over $7 billion is spent annually in the US to treat falls in older adults4

1Kenny RA, Kapoor WN. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:23-27.2OutPatientView v. 6.0. Solucient LLC, Evanston IL.3Farwell D, et al. J Cardiovasc Electrophysiol. 2002;13(Supp):S9-S13.4Olshansky B. In: Grubb B and Olshansky B. eds. Syncope: Mechanisms and Management. Futura. 1998:15-71.

Impact of Syncope: Quality of Life

1Linzer M. J Clin Epidemiol. 1991;44:1037.2Linzer M. J Gen Int Med. 1994;9:181.

0

20

40

60

80

100

Anxiety/Depression

Alter DailyActivities

RestrictedDriving

ChangeEmployment

73%171%2

60%2

37%2

Per

cen

t o

f P

atie

nts

Quality of Life: UK Population Norms vs. Syncope Patients

Rose M, et al. J Clin Epidemiol. 2000;53:1209-1216.

0

10

20

30

40

50 UK Population Norms

Patients with Syncope

3%

26%

4%

37%

1%

9%

36%

49%

19%

43%

Mobility Usual Activities

Self-Care Pain/Discomfort

Anxiety/Depression

% P

reva

len

ce

Syncope Mortality

Low 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]

Implications of Syncope for Driving a Vehicle

Those who drive and have recurrent syncope risk their lives and the lives of others

Places considerable burden on the physician

Essential to know local laws and physician responsibilities

Some states – Invasion of privacy to notify motor vehicle department*

• Other states – Reporting is mandatory*

If the patient has sufficient warning of impending syncope – Driving may be permitted

Olshansky B, Grubb B. In: Syncope: Mechanisms and Management. Futura. Armonk, NY. 1998.*Medtronic, Inc. Follow-up Forum. 1995/96;1(3):8-10.

Challenges of Syncope

Diagnosis

• Complex

Quality of life implications

• Work

• Mobility (automobiles)

• Psychological

Cost

• Cost/year

• Cost/diagnosis

Section II:

Diagnosis

Diagnostic Objectives

Distinguish true syncope from syncope mimics

Determine presence of heart disease

Establish the cause of syncope with sufficient certainty to:

• Assess prognosis confidently

• Initiate effective preventive treatment

A Diagnostic Plan is Essential

Initial Examination• Detailed patient history• Physical exam• ECG• Supine and upright

blood pressure Monitoring

• Holter• Event• Insertable Loop Recorder (ILR)

Cardiac Imaging Special Investigations

• Head-up tilt test• Hemodynamics • Electrophysiology study


Diagnostic Flow Diagram for TLOC


Initial EvaluationInitial Evaluation

TreatmentTreatment

SyncopeSyncope Not SyncopeNot Syncope

Certain Diagnosis

Certain Diagnosis

Unexplained Syncope

Unexplained Syncope

Cardiac Likely

Cardiac Likely

Cardiac Tests

Cardiac Tests

Neurally-Mediated or Orthostatic Likely

Neurally-Mediated or Orthostatic Likely

Tests for Neurally-Mediated SyncopeTests for Neurally-Mediated Syncope

Frequent or Severe Episodes

Frequent or Severe Episodes

Tests for Neurally-Mediated SyncopeTests for Neurally-Mediated Syncope

Single/Rare Episodes

Single/Rare Episodes

No Further EvaluationNo Further Evaluation

Confirm with Specific Test or

Specialist Consultation

Confirm with Specific Test or

Specialist Consultation

Suspected DiagnosisSuspected Diagnosis

+ - + - + -

TreatmentTreatment TreatmentTreatment

Re-AppraisalRe-AppraisalRe-AppraisalRe-Appraisal

TreatmentTreatment

Initial Exam: Detailed Patient History

Circumstances of recent event• Eyewitness account of event• Symptoms at onset of event• Sequelae• Medications

Circumstances of more remote events

Concomitant disease, especially cardiac

Pertinent family history• Cardiac disease• Sudden death• Metabolic disorders

Past medical history• Neurological history• Syncope


Initial Exam: Thorough Physical

Vital signs

• Heart rate

• Orthostatic blood pressure change

Cardiovascular exam: Is heart disease present?

• ECG: Long QT, pre-excitation, conduction system disease

• Echo: LV function, valve status, HCM

Neurological exam

Carotid sinus massage

• Perform under clinically appropriate conditions preferably during head-up tilt test

• Monitor both ECG and BP


Carotid Sinus Massage (CSM)

Method1

• Massage, 5-10 seconds

• Don’t occlude

• Supine and upright posture (on tilt table)

Outcome

• 3 second asystole and/or 50 mmHg fall in systolic BP with reproduction of symptoms = Carotid Sinus Syndrome

Absolute contraindications2

• Carotid bruit, known significant carotid arterial disease, previous CVA, MI last 3 months

Complications

• Primarily neurological

• Less than 0.2%3

• Usually transient

1Kenny RA. Heart. 2000;83:564.2Linzer M. Ann Intern Med. 1997;126:989.3Munro N, et al. J Am Geriatr Soc. 1994;42:1248-1251.

Other Diagnostic Tests

Ambulatory ECG

• Holter monitoring

• Event recorder

− Intermittent vs. Loop

− Insertable Loop Recorder (ILR)

Head-Up Tilt (HUT)

• Includes drug provocation (NTG, isoproterenol)

• Carotid Sinus Massage (CSM)

Adenosine Triphosphate Test (ATP)

Electrophysiology Study (EPS)


Heart Monitoring Options

ILR

Event Recorders(non-lead and loop)

Holter Monitor

12-Lead

2 Days

7-30 Days

Up to 14 Months

10 Seconds

OPTION

TIME (Months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14


Diagnostic Assessment: Yields (N=3411 to 4332)

References Available

Yield (%)

Initial Evaluation

History, Physical Exam, ECG, Cardiac Massage38-40

Other Tests/Procedures

Head-Up Tilt 27

External Cardiac Monitoring 5-13

Insertable Loop Recorder (ILR) 43-883-5

EP Study <2-5

Exercise Test 0.5

EEG 0.3-0.5

MRINo data

available6

Neurological Tests: Rarely Diagnostic for Syncope

EEG, Head CT, Head MRI

May help diagnose seizure

Brignole M, et al. Europace. 2004;6:467-537.

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


60° - 80°

Head-up Tilt Test

Carlos Morillo, MD, FRCPCProfessor, Faculty of Health SciencesMcMaster University, Hamilton Ontario

Click once on image to play video.

Head-Up Tilt Test:ECG Leads and Intra-Arterial Pressure Tracing

DG Benditt, MD. U of M Cardiac Arrhythmia Center

2

1

Adenosine Triphosphate (ATP) Test

Ongoing investigation in the US

Provokes a short and potent cardioinhibitory vasovagal response

Advantages

• Simple

• Inexpensive

• Correlation with pacing benefit

Seems to identify a unique mechanism of syncope found in patients with:

• Advanced age

• More hypertension

• More ECG abnormalities

Brignole M. Heart. 2000;83:24-28. Donateo P. J Am Coll Cardiol. 2003;41:93-98.Flammang D. Circ. 1999;99:2427-2433.

Reveal® Plus ILR

Insertable Loop Recorder (ILR)

Typical Location of theReveal® Plus ILR

Click once on black screen to play video.


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


Click once on black screen to play video.

Symptom-Rhythm Correlation with the ILR

CASE: 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.

Randomized Assessment of Syncope Trial (RAST)

Results: Combining primary strategy with crossover, the diagnostic yield is

43% ILR only vs. 20% conventional only1

Cost/diagnosis is 26% less than conventional testing2

1Krahn AD, et al. Circ. 2001;104:46-51. 2Krahn AD, et al. JACC. 2003;42:495-501.

Unexplained Syncope

EF > 35%

60 Patients

AECG, Tilt,EP Study

Diagnosis

ILR

++

–++

–

ILRConventional

Testing(AECG, Tilt, EPS)

30 Patients 30 Patients

PrimaryStrategy

Crossover

14 6

1 8

++ ++

Conventional EP Testing in Syncope

Greater diagnostic value in older patients or those with SHD

Less diagnostic value in healthy patients without SHD

Useful diagnostic observations:

• Inducible monomorphic VT

• SNRT > 3000 ms or CSNRT > 600 ms

• Inducible SVT with hypotension

• HV interval ≥ 100 ms (especially in absence of inducible VT)

• Pacing induced infra-nodal block

Benditt D. In: Topol E, ed. Textbook of Cardiovascular Medicine. Lippencott;2002:1529-1542.Lu F, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.Brignole M, et al. Europace. 2004;6:467-537.

Diagnostic Limitations of EPS

Difficult to correlate spontaneous events and laboratory findings

Positive findings1

• Without SHD: 6-17%

• With SHD: 25-71%

Less effective in assessing bradyarrhythmias than tachyarrhythmias2

EPS findings must be consistent with clinical history

• Beware of false positive

1Linzer M, et al. Ann Int Med. 1997;127:76-86.2Lu F, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;80-95.

ISSUEInternational Study of Syncope of Uncertain Etiology

Multicenter, international, prospective study

Analyzed the diagnostic contribution of an ILR in three predefined groups of patients with syncope of uncertain origin:

1) Isolated syncope: No SHD, Normal ECG1

• Negative tilt

• Positive tilt

2) Patients with heart disease and negative EP test2

3) Patients with bundle branch block and negative EP test3

1Moya A. Circulation. 2001; 104:1261-1267. 2Menozzi C, et al. Circulation. 2002;105:2741-2745.3Brignole M, et al. Circulation. 2001;104:2045-2050.

ISSUEPatients with Isolated Syncope and Tilt-Positive Syncope

Moya A. Circulation.

2001;104:1261-1267.

Follow-Up to Recurrent Spontaneous Episode

111 Patients with Syncope No SHD, Normal ECG

29: Tilt-Positive 82: Tilt-Negative “Isolated Syncope”

Tilt Test Followed byInsertable Loop Recorder

ISSUEIsolated Syncope vs. Tilt-Positive Syncope

Conclusions

Results similar in the two arms, including syncope recurrence and ECG correlation

Tilt-negative patients had as many bradycardias (18%) astilt-positive patients (21%)

Most frequent finding was asystole secondary to progressive sinus bradycardia, suggesting a neuro-mediated origin

Homogeneous findings from tilt-negative and tilt-positive infer low sensitivity of tilt-testing

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

ISSUE Patients with Heart Disease and a Negative EP Test

Menozzi C, et al. Circulation. 2002;105:2741-2745.

35 Pts with Heart Diseaseand Insertable Loop Recorder

Syncope: 6 Pts (17%)

ECG-Documented: 6 Pts (17%)

Pre-Syncope: 13 Pts (37%)

ECG-Documented: 8 Pts (23%)

AV block + asystole: 1A.Fib + asystole: 1Sinus arrest: 1Sinus tachycardia: 1Rapid A.Fib: 2

Sustained VT: 1Parox. A.Fib/AT: 1Post tachycardia pause: 1No rhythm variations: 4Sinus tachycardia: 1

ISSUEPatients with Heart Disease and a Negative EP Test

Conclusions

Patients with unexplained syncope, overt heart disease, and negative EP study had a favorable medium-term outcome

Mechanism of syncope was heterogeneous

Ventricular tachyarrhythmia was unlikely

“ILR-guided strategy seems reasonable, with specific therapy safely delayed until a definite diagnosis is made.”

Menozzi C, et al. Circulation. 2002;105:2741-2745.

ISSUEPatients with Bundle Branch Block and Negative EP Test

Brignole M., ET AL.,Circulation. 2001;104:2045-2050. * 5 of these also had ≥1 presyncope** Drop-out before primary-end point

52 Pts with BBBand Insertable Loop Recorder

Syncope: 22 Pts (42%)*

ILR-Detected: 19

AVB: 12 (63%)SA: 4 (21%)Asystole-undefined: 1 (5%)NSR: 1 (5%)Sinus tachy: 1 (5%)

Not Detected: 3

Stable AVB: 3 Pts (6%)

ILR-DetectedPre-Syncope:2 Pts (4%)**

Death: 1 Pt (2%)

AVB: 2 (4%)

ISSUEPatients with Bundle Branch Block and Negative EP Test

Conclusion:

In patients with BBB and negative EP study, most syncopal recurrences have a homogeneous mechanism that is characterized by prolonged asystolic pauses mainly attributable to sudden-onset paroxysmal AV block

Brignole M. Circulation. 2001;104:2045-2050.

Section III:

Specific Conditions and Treatment

Specific Conditions

Cardiac arrhythmia

• Brady/Tachy

• Long QT syndrome

• Torsade de pointes

• Brugada

• Drug-induced

Structural cardio-pulmonary

Neurally-mediated

• Vasovagal Syncope (VVS)

• Carotid Sinus Syndrome (CSS)

Orthostatic

Cardiac Syncope

Includes cardiac arrhythmias and SHD

Often life-threatening

May be warning of critical CV disease

• Tachy and brady arrhythmias

• Myocardial ischemia, aortic stenosis, pulmonary hypertension, aortic dissection

Assess culprit arrhythmia or structural abnormality aggressively

Initiate treatment promptly


“…cardiac syncope can be a harbinger of sudden death.”

Survival with and without syncope

6-month mortality rate of greater than 10%

Cardiac syncope doubled the risk of death

Includes cardiac arrhythmias and SHD

No SyncopeVasovagal andOther CausesCardiac Cause

0 5 1015 Follow-Up (yr)

Pro

bab

ility

of

Sur

viva

l

1.0

0.8

0.6

0.4

0.2

0.0

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

Syncope Due to Structural Cardiovascular Disease: Principle Mechanisms

Acute MI/Ischemia

• 2° neural reflex bradycardia – Vasodilatation, arrhythmias, low output (rare)

Hypertrophic cardiomyopathy

• Limited output during exertion (increased obstruction, greater demand), arrhythmias, neural reflex

Acute aortic dissection

• Neural reflex mechanism, pericardial tamponade

Pulmonary embolus/pulmonary hypertension

• Neural reflex, inadequate flow with exertion

Valvular abnormalities

• Aortic stenosis – Limited output, neural reflex dilation in periphery

• Mitral stenosis, atrial myxoma – Obstruction to adequate flow


Syncope Due to Cardiac Arrhythmias

Bradyarrhythmias

• Sinus arrest, exit block

• High grade or acute complete AV block

• Can be accompanied by vasodilatation (VVS, CSS)

Tachyarrhythmias

• Atrial fibrillation/flutter with rapid ventricular rate (eg, pre-excitation syndrome)

• Paroxysmal SVT or VT

• Torsade de pointes


ILR Recordings

CASE: 28 year-old man presents to ER multiple times after falls resulting in trauma. VT: Ablated and medicated.

CASE: 83 year-old woman with syncope due to bradycardia: Pacemaker implanted.

Reveal ® ILR recordings; Medtronic data on file.

Cardiac Rhythms During Unexplained Syncope

Seidl K. Europace. 2000;2(3):256-262.Krahn AD. PACE. 2002;25:37-41.Medtronic ILR Replacement Data. FY03, 04. On file.

No Recurrence 36%

(31-48%)

Normal Sinus Rhythm 31%

(17-44%)

Other 11%

Arrhythmia 22%

(13-32%)

Tachycardia 6%(2-11%)

Bradycardia 16%

(11-21%)

Composite: N=133 to 7109

Long QT Syndromes

Mechanism

• Abnormalities of sodium and/or potassium channels

• Susceptibility to polymorphic VT (Torsade de pointes)

Prevalence

• Drug-induced forms – Common

• Genetic forms – Relatively rare, but increasingly being recognized

• “Concealed” forms:

− May be common

− Provide basis for drug-induced torsade

Schwartz P, Priori S. In: Zipes D and Jalife J, eds. Cardiac Electrophysiology. Saunders;2004:651-659.

Syncope: Torsade de Pointes

From the files of DG Benditt, MD. U of M Cardiac Arrhythmia Center

Long QT Syndromes: 12-Lead ECG


Drug-Induced QT Prolongation(List is continuously being updated)

Antiarrhythmics

• Class IA ...Quinidine, Procainamide, Disopyramide

• Class III…Sotalol, Ibutilide, Dofetilide, Amiodarone, NAPA*

Antianginal Agents

• Bepridil*

Psychoactive Agents

• Phenothiazines, Amitriptyline, Imipramine, Ziprasidone

Antibiotics

• Erythromycin, Pentamidine, Fluconazole, Ciprofloxacin and its relatives

Nonsedating antihistamines

• Terfenadine*, Astemizole

Others

• Cisapride*, Droperidol, Haloperidol

*Removed from U.S. Market


Treatment of Long QT

Suspicion and recognition are critical

Emergency treatment

• Intravenous magnesium

• Pacing to overcome bradycardia or pauses

• Isoproterenol to increase heart rate and shorten repolarization

• ICD if prior SCA or strong family history

• If drug induced:

− Reverse bradycardia

− Withdraw drug

− Avoid ALL long-QT provoking agents

• If genetic:

− Avoid ALL long-QT provoking agents

For more information visit www.longqt.orgSchwartz P, Priori S. In: Zipes D and Jalife J, eds. Cardiac Electrophysiology. Saunders;2004:651-659.

Treatment of Syncope Due to Bradyarrhythmia

Class I indication for pacing using dual chamber system wherever possible

Ventricular pacing in atrial fibrillation with slow ventricular response

ACC/AHA/NASPE 2002 Guideline Update. Circ. 2002;106:2145-2161.

nV

0.4

0.2

0.0

-0.2

-0.4

:45:44:43:42:41:40:39:38:37

:37:36:35:34:33:32:31:30:29

:29:28:27:26:25:24:23:22:21

08:23:21

8:23:29

08:23:37

0.4

0.2

0.0

-0.2

-0.4

0.4

0.2

0.0

-0.2

-0.4

Treatment of Syncope Due to Tachyarrhythmia

Atrial tachyarrhythmias

• AVRT due to accessory pathway – Ablate pathway

• AVNRT – Ablate AV nodal slow pathway

• Atrial fib – Pacing, linear/focal ablation for paroxysmal AF

• Atrial flutter – Ablate the IVC-TV isthmus of the re-entrant circuit for ‘typical’ flutter

Ventricular tachyarrhythmias

• Ventricular tachycardia – ICD or ablation where appropriate

• Torsade de pointes – Withdraw offending drug or implant ICD (long QT/Brugada/short QT)

Drug therapy may be an alternative in many cases


Neurally-Mediated Reflex Syncope

Vasovagal Syncope (VVS)

Carotid Sinus Syndrome (CSS)

Situational syncope

• Post-micturition

• Cough

• Swallow

• Defecation

• Blood drawing, etc.


Pathophysiology

Autonomic Nervous System

Benditt D, et al. Neurally mediated syncope: Pathophysiology, investigations and treatment. Blanc JJ, et al. eds. Futura. 1996.

VVSClinical Pathophysiology

Neurally-mediated physiologic reflex mechanism with two components:

1. Cardioinhibitory (↓ HR)

2. Vasodepressor (↓ BP) despite heart beats, no significant BP generated

Both components are usually present

Wieling W, et al. In: Benditt D, et al. The Evaluation and Treatment of Syncope. Futura. 2003;11-22.

1

2

VVSIncidence

Most common form of syncope

• 8% to 37% (mean 18%) of syncope cases

Depends on population sampled

• Young without SHD, ↑ incidence

• Older with SHD, ↓ incidence

Linzer M, et al. Ann Intern Med. 1997;126:989.

VVS vs. CSS

In general:

• VVS patients younger than CSS patients

• Ages range from adolescence to older adults (median 43 years)

Linzer M, et al. Ann Intern Med. 1997;126:989.

VVS Recurrences

1Savage D, et al. STROKE. 1985;16:626-29. 2Sheldon R, et al. Circulation. 1996;93:973-81.

35% of patients report syncope recurrence during follow-up ≤3 years1

Positive HUT with >6 lifetime syncope episodes: recurrence risk >50% over 2 years2

1000

800

50

100

25

8

4

2

1

1 2 3 6 24 84 480

Months Since Symptoms Began

Two Year Risk

Tot

al N

umbe

r of

Syn

copa

l Epi

sode

s

> 75%

50-75%

25-50%

< 25%


16.3

sec

Continuous Tracing 1 sec

VVS Spontaneous

16 year-old male, healthy, athletic, monitored for fainting.

VVSDiagnosis

History and physical exam, ECG and BP

Head-Up Tilt (HUT) – Protocol:

• Fast > 2 hours

• ECG and continuous blood pressure, supine, and upright

• Tilt to 70°, 20 minutes

• Isoproterenol/Nitroglycerin if necessary

• End point – Loss of consciousness

60° - 80°

Benditt D, et al. JACC. 1996;28:263-275.Brignole M, et al. Europace, 2004;6:467-537.

VVS General Treatment Measures

Optimal treatment strategies for VVS are a source of debate

Treatment goals

• Acute intervention− Physical maneuvers, eg,

crossing legs or tugging arms

− Lowering head

− Lying down

Long-term prevention

• Tilt training

• Education

• Diet, fluids, salt

• Support hose

• Drug therapy

• Pacing


VVS Tilt Training Protocol

Objectives

• Enhance orthostatic tolerance

• Diminish excessive autonomic reflex activity

• Reduce syncope susceptibility/recurrences

Technique

• Prescribed periods of upright posture against a wall

• Start with 3-5 min BID

• Increase by 5 min each week until a duration of 30 min is achieved

Reybrouck T, et al. PACE. 2000;23(4 Pt. 1):493-498.

VVS Tilt Training: Clinical Outcomes

Treatment of recurrent VVS

Reybrouck, et al.*: Long-term study

• 38 patients performed home tilt training

• After a period of regular tilt training, 82% remained free of syncope during the follow-up period

• However, at the 43-month follow-up, 29 patients had abandoned the therapy

• Conclusion: The abnormal autonomic reflex activity of VVS can be remedied. Compliance may be an issue.

*Reybrouck T, et al. PACE. 2000;23:493-498.

VVS Tilt Training: Clinical Outcomes

Foglia-Manzillo, et al.*: Short-term study

• 68 patients

– 35 tilt training

– 33 no treatment (control)

• Tilt table test conducted after 3 weeks

• 19 (59%) of tilt trained and 18 (60%) of controls had a positive test

• Tilt training was not effective in reducing tilt testing positivity rate

• Poor compliance in the majority of patients with recurrent VVS

*Foglio-Manzillo G, et al. Europace. 2004;6:199-204.

VVS Pharmacologic Treatment

Fludrocortisone

Beta-adrenergic blockers

• Preponderance of clinical evidence suggests minimal benefit1

SSRI (Selective Serotonin Re-Uptake Inhibitor)

• 1 small controlled trial2

Vasoconstrictors

• 1 negative controlled trial (etilefrine)3

• 2 positive controlled trials (midodrine)4,5

1Brignole M, et al. Europace, 2004;6:467-537.2Di Girolamo E, et al. JACC. 1999;33:1227-1230.3Raviele A, et al. Circ. 1999;99:1452-1457.

4Ward C, et al. Heart. 1998;79:45-49.5Perez-Lugones A, et al. J Cardiovasc Electrophysiol. 2001;12(8):935-938.

Midodrine for VVS

Perez-Lugones A, Schweikert R, Pavia S, et al. J Cardiovasc Electrophysiol. 2001;12(8):935-938.

Months

p < 0.001

Sym

pto

m-F

ree

Inte

rval

180160140120100806040200

100

80

60

40

20

0

Fluid

Midodrine

The Role of Pacing as Therapy for Syncope

VVS with +HUT and cardioinhibitory response:Class IIb indication for pacing

Three randomized, prospective trials reported benefits of pacing in select VVS patients:

• VPS I1

• VASIS2

• SYDIT3

Subsequent study results less clear

• VPS II4

• Synpace5

• INVASY6

1Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.2Sutton R. Circulation. 2000;102:294-299.3Ammirati F. Circ. 2001;104:52-57.

4Connolly S. JAMA. 2003;289:2224-2229.5Giada F. PACE . 2003;26:1016 (abstract).6Occhetta E, et al. Europace. 2004;6:538-547.

VPS I (North American Vasovagal Pacemaker Study)

Objective: To evaluate pacemaker therapy for severe recurrent vasovagal syncope

Randomized, prospective, single center

N=54 patients

• 27: DDD pacemaker with rate drop response

• 27: No pacemaker

Inclusion: Vasodepressor response

Primary outcome: First recurrence of syncope

Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.

100

90

80

70

60

50

40

30

20

10

0

0 3 6 9 12 15

Time in Months

No Pacemaker (PM)

2P=0.000022

PacemakerCu

mu

lati

ve R

isk

(%)

Connolly SJ. J Am Coll Cardiol. 1999;33:16-20.

Results: 6 (22%) with PM had recurrence vs. 19 (70%) without PM 84% RRR (2p=0.000022)

VPS I (North American Vasovagal Pacemaker Study)

VASIS (VAsovagal Syncope International Study)

Objective: To evaluate pacemaker therapy for severe cardioinhibitory tilt-positive neurally mediated syncope

Randomized, prospective, multi-center

N=42 patients

• 19: DDI pacemaker (80 bpm) with rate hysteresis (45 bpm)

• 23: No pacemaker

Inclusion: Positive cardioinhibitory response


Sutton R. Circulation. 2000;102:294-299.

Sutton R. Circulation. 2000;102:294-299.

Pacemaker (PM)

No Pacemaker

p=0.0004

Years

% S

ynco

pe-

Fre

e

100

80

60

40

20

0 2 3 4 5 6

Results: 1 (5%) with PM had recurrence vs. 14 (61%) without PM

VASIS (VAsovagal Syncope International Study)

SYDIT (SYncope DIagnosis and Treatment)

Objective: To compare the effects of cardiac pacing with pharmacological therapy in patients with recurrent vasovagal syncope

Randomized, prospective, multi-center

N=93 patients


• 47: Atenolol 100 mg/d

Inclusion: Positive HUT with relative bradycardia


Ammirati F. Circulation. 2001;104:52-57.

SYDIT (SYncope DIagnosis and Treatment)

Ammirati F. Circulation. 2001;104:52-57.

0.6

0.7

0.8

0.9

1.0

0 100 200 300 400 500 600 700 800 900 1000

Drug

Pacemaker (PM)

Time (Days)

% S

ynco

pe-

Fre

e

p=0.0032

Results: 2 (4%) with PM had syncope recurrence vs. 12 (26%) without PM

VPS II (Vasovagal Pacemaker Study II)

Objective: To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope

Randomized, double-blind, prospective, multi-center

N=100 patients

• 52: Only sensing without pacing


Inclusion: Positive HUT with (HRxBP) < 6000/min x mm Hg


Connolly S. JAMA. 2003;289:2224-2229.

Dual Chamber Pacing (DDD)

Only Sensing Without Pacing (ODO)

1.0

0.8

0.6

0.4

0.2

0

Months Since Randomization

Cu

mu

lati

ve R

isk

6543210

Connolly S. JAMA. 2003;289:2224–2229.

Results: 33% with pacing had recurrence vs. 42% with only sensing

(not statistically significant)

VPS II (Vasovagal Pacemaker Study II)

SYNPACE(Vasovagal SYNcope and PACing)

Objective: To determine if pacing therapy will reduce syncope relapses in patients with recurrent vasovagal syncope, compared to those with a pacemaker programmed to OFF

Randomized, double-blind, prospective, multi-center, placebo-controlled

N=29 patients

• 16: DDD PM with rate drop response programmed ON

• 13: PM programmed OFF (OOO mode)

Inclusion: Recurrent VVS and +HUT with asystolic or mixed response


Raviele A.. Europace. 2001;3:336–341.Raviele A, et al. Eur Heart J. 2004;25:1741-1748.

SYNPACE(Vasovagal SYNcope and PACing)

Raviele A, et al. Eur Heart J. 2004;25:1741-1748.

Results: 50% with pacing ON had recurrence vs. 38% with pacing OFF

(not statistically significant)

0.6

0.7

0.8

0.9

1.0

0 200 400 600 800 1000

Pacemaker OFF

% S

ynco

pe-

Fre

e

p=0.58

0.5

0.4

0.3

0.2

0.1

0.0

Pacemaker ON

Days Since Randomization

INVASY(INotropy Controlled Pacing in VAsovagal Syncope)

Objective: To evaluate Closed Loop Stimulation (CLS), a form of rate-adaptive pacing using RV impedance, in preventing recurrence of VVS

Randomized, prospective, single-blind, multi-center

N=50 patients

• 41: CLS therapy

• 9: Control (pacemaker programmed in DDI)

Inclusion: Recurrent VVS and +HUT with cardioinhibition

Primary outcome: Recurrence of two VVSs during a minimum of 1 year of follow-up

Occhetta E, et al. Europace. 2004;6:538-547.

INVASY(INotropy Controlled Pacing in VAsovagal SYncope)

20

40

60

0

100

% S

ynco

pe-

Fre

e

P < 0.0001

Closed Loop Stimulation (CLS)

Control (DDI only)

Time Since Randomization

3m 6m 9m 1y 2y 3y

Results: Patients with CLS had no syncope recurrence and improved quality of life

Occhetta E, et al. Europace. 2004;6:538-547.

Role of Pacing as Therapy for Syncope: Summary

Three earlier studies single blind – Bias?

Pacemaker implantation may modulate reflex syncope and autonomic responses1

Study results may differ based on pre-implant selection criteria and tilt-testing techniques

Pacing therapy is effective in some but not all (cardioinhibition vs. vasodepression)

In five pacing studies, syncope recurred in 33/156 (21%) of paced patients, 72/162 (44%) in non-paced patients (p<0.000)2

1Kapoor W. JAMA. 2003;289:2272-2275.2Brignole M, et al.. Europace. 2004;6:467-537.

CSSCarotid Sinus Syndrome

Syncope 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 symptoms

• No treatment

Kenny RA, et al. J Am Coll Cardiol. 2001;38:1491-1496.Brignole M, et al. Europace. 2004;6:467-537.Sutton R. In: Neurally Mediated Syncope: Pathophysiology, Investigation and Treatment. Blanc JJ, et al. eds. Armonk, NY: Futura;1996:138.

CSSEtiology

Sensory nerve endings in the carotid sinus walls respond to deformation

“Deafferentation” of neck muscles may contribute

Increased afferent signals tobrain stem

Reflex increase in efferent vagal activity and diminution of sympathetic tone results in bradycardia and vasodilatation

Carotid Sinus

Falls:Incidence, Recurrence, CSH*

1 J Am Geriatr Soc. 1995.2 Richardson D, et al. PACE. 1997;20:820.

0

25

50

75

Incidence> Age 65

Recurrence CSH* Presentin Fallers > Age 50Presenting at ER

30% 1

50% 1

23% 2

% o

f P

op

ula

tio

n

*Carotid Sinus Hypersensitivity

0

25

50

75

No Pacing Pacing

57%

%6

% R

ecu

rren

ce

CSS Role of Pacing – Syncope Recurrence Rate

Class I indication for pacing (AHA and BPEG)

Limit pacing to CSS that is:

• Cardioinhibitory

• Mixed

DDD/DDI superior to VVI

• Mean follow-up = 6 months

Brignole M, et al. Eur JCPE. 1992;4:247-254.

SAFE PACESyncope And Falls in the Elderly – Pacing And Carotid Sinus Evaluation

Objective

• Determine whether cardiac pacing reduces falls in older adults with carotid sinus hypersensitivity

Randomized controlled trial (N=175)

• Adults > 50 years, non-accidental fall, positive CSM

• Pacing (n=87) vs. No Pacing (n=88)

Results

• More than 1/3 of adults over 50 years presented to the Emergency Department because of a fall

• With pacing, falls 70%

• Syncopal events 53%

• Injurious events 70%

Kenny RA. J Am Coll Cardiol. 2001;38:1491-1496.

SAFE PACE

Conclusions

• Strong association between non-accidental falls and cardioinhibitory CSH

• These patients usually not referred for cardiac assessment

• Cardiac pacing significantly reduced subsequent falls

• CSH should be considered in all older adults who have non-accidental falls

Kenny RA, J Am Coll Cardiol. 2001; 38:1491-1496.

Orthostatic Hypotension

Etiology

Drug-induced (very common)

• Diuretics

• Vasodilators

Primary autonomic failure

• Multiple system atrophy

• Parkinson’s Disease

• Postural Orthostatic Tachycardia Syndrome (POTS)

Secondary autonomic failure

• Diabetes

• Alcohol

• Amyloid


Treatment Strategies for Orthostatic Intolerance

Patient education, injury avoidance

Hydration

• Fluids, salt, diet

• Minimize caffeine/alcohol

Sleeping with head of bed elevated

Tilt training, leg crossing, arm pull

Support hose

Drug therapies

• Fludrocortisone, midodrine, erythropoietin

Tachy-Pacing (probably not useful)


Section IV:

Special Issues

Syncope: Diagnostic Testing in Hospital Strongly Recommended

Suspected/known ‘significant’ heart disease

ECG abnormalities suggesting potential life-threatening arrhythmic cause

Syncope during exercise

Severe injury or accident

Family history of premature sudden death


SEEDS: Syncope Evaluation in the Emergency Department Study

Survival Free from Death

Shen W, et al. Circ. 2004;110(24):3636-3645.

Survival Free from Recurrence

Long-Term Clinical Outcomes

100%

90%

80%

70%

Years

210

P=0.30

Syncope Unit Group

Standard Care Group

100%

90%

80%

70%

Years

210

P=0.72

Syncope Unit Group

Standard Care Group

Results: Syncope unit improved diagnostic yield in the ED and reduced

hospital admission and length of stay

The Integrated Syncope Unit

To optimize the effectiveness of the evaluation and treatment of syncope patients at a given center

Best accomplished by:

• Cohesive, structured care pathway

• Multidisciplinary approach

• Core equipment available

• Preferential access to other tests or therapy

Majority of syncope evaluations – Out-patient or day cases

1Kenny RA, Brignole M. In: Benditt D, et al. eds. The Evaluation and Treatment of Syncope. Futura;2003:55-60. 2Brignole M, et al. Europace, 2004;6:467-537.

Conclusion

Syncope is a common symptom with many causes

Deserves thorough investigation and appropriate treatment

A disciplined approach is essential

ESC guidelines offer current best practices


Challenges of Syncope

Cost

Quality of life implications

Diagnosis and treatment

• Diagnostic yield and repeatability of tests

• Frequency and clustering of events

• Difficulty in managing/treating/controlling future events

• Appropriate risk stratification

• Complex etiology

Olshansky B. In: Grubb B and Olshansky B. eds. Syncope: Mechanisms and Management. Futura. 1998:15-71.Brignole M, et al. Europace, 2004;6:467-537.

Brief Statement

Indications

9526 Reveal® Plus Insertable Loop Recorder

The Reveal Plus 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

6191 Activator

The Model 6191 Activator is intended for use in combination with a Medtronic Model 9526 Reveal Plus Insertable Loop Recorder.

Contraindications

There are no known contraindications for the implantation of the Reveal Plus ILR. However, the patient’s particular medical condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated.

Warnings/Precautions

9526 Reveal Plus Insertable Loop Recorder

Patients with the Reveal Plus ILR should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation to avoid electrical reset of the device, and/or inappropriate sensing.

6191 Activator

Operation of the Model 6191 Activator near sources of electromagnetic interference, such as cellular phones, computer monitors, etc., may adversely affect the performance of this device.

Potential Complications

Potential complications include, but are not limited to, body tissue rejection phenomena, including local tissue reaction, infection, device migration and erosion of the device through the skin.

2090 Programmer

The Medtronic/Vitatron CareLink programmer system is comprised of prescription devices indicated for use in the interrogation and programming of implantable medical devices. Prior to use, refer to the Programmer Reference Guide as well as the appropriate programmer software and implantable device technical manuals for more information related to specific implantable device models. Programming should be attempted only by appropriately trained personnel after careful study of the technical manual for the implantable device and after careful determination of appropriate parameter values based on the patient's condition and pacing system used. The Medtronic/Vitatron CareLink programmer must be used only for programming implantable devices manufactured by Medtronic or Vitatron.

See the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential complications/adverse events. For further information, please call Medtronic at 1-800-328-2518 and/or consult Medtronic’s website at www.medtronic.com. To learn more about syncope, visit www.fainting.com.

Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.

Documents

Syncope A Diagnostic and Treatment Strategy David G. Benditt, M.D. University of Minnesota Medical School Minneapolis, MN USA Richard Sutton, DScMed Royal