SyncopeDxTxStrategy[1]

Syncope

A Diagnostic and Treatment Strategy

Developed by:David G. Benditt, M.D. Richard Sutton, DScMedUniversity of Minnesota Medical Center Royal Brompton Hospital, London, UK

Presentation Overview

I. Prevalence & ImpactII. EtiologyIII. Diagnosis & Evaluation OptionsIV. Specific ConditionsV. Treatment OptionsVI. Insights into more efficient and effective

diagnosis and treatment of patients with syncope

Section I:

Prevalence and Impact

The Significance of Syncope

The only difference between

syncope and sudden death is that in one you wake up.1

1 Engel GL. Psychologic stress, vasodepressor syncope, and sudden death. Ann Intern Med 1978; 89: 403-412.


1 National Disease and Therapeutic Index on Syncope and Collapse, ICD-9-CM 780.2, IMS America, 19972 Blanc J-J, L’her C, Touiza A, et al. Eur Heart J, 2002; 23: 815-820.3 Day SC, et al, AM J of Med 19824 Kapoor W. Evaluation and outcome of patients with syncope. Medicine 1990;69:160-175

Individuals <18 yrs

Military Population 17- 46 yrs

Individuals 40-59 yrs*

Individuals >70 yrs*

15%

20-25%

16-19%

23%

Syncope Reported Frequency

*during a 10-year periodBrignole M, Alboni P, Benditt DG, et al. Eur Heart J, 2001; 22: 1256-1306.


500,000 new syncope patients each year 5

170,000 have recurrent syncope 6

70,000 have recurrent, infrequent, unexplained syncope 1-4

explained: 53% to 62%

infrequent, unexplained: 38% to 47% 1-4

1 Kapoor W, Med. 1990;69:160-175.2 Silverstein M, et al. JAMA. 1982;248:1185-1189.3 Martin G, et al. Ann Emerg. Med. 1984;12:499-504.

4 Kapoor W, et al. N Eng J Med. 1983;309:197-204.5 National Disease and Therapeutic Index, IMS America, Syncope and Collapse #780.2; Jan 1997-Dec 1997.6 Kapoor W, et al. Am J Med. 1987;83:700-708.

1 Day SC, et al. Am J of Med 1982;73:15-23.2 Kapoor W. Medicine 1990;69:160-175.3 Silverstein M, Sager D, Mulley A. JAMA. 1982;248:1185-1189.4 Martin G, Adams S, Martin H. Ann Emerg Med. 1984;13:499-504.

Some causes of syncope are potentially fatal Cardiac causes of syncope have the highest mortality

rates


0%

5%

10%

15%

20%

25%

Sync

ope

Mor

talit

y

Overall Due to Cardiac Causes

Impact of Syncope

11Linzer, Linzer, J Clin EpidemiolJ Clin Epidemiol, 1991., 1991.22Linzer, Linzer, J Gen Int MedJ Gen Int Med, 1994., 1994.

0%

20%

40%

60%

80%

100%

Anxiety/Depression

Alter DailyActivities

RestrictedDriving

ChangeEmployment

73% 171% 2

60% 2

37% 2

Pro

porti

on o

f Pat

ient

s

Section II:

Etiology

Syncope: A Symptom…Not a Diagnosis

Self-limited loss of consciousness and postural tone

Relatively rapid onset Variable warning symptoms Spontaneous complete recovery

Cause Prevalence (Mean) %

Prevalence (Range) %

Reflex-mediated:Vasovagal 18 8-37Situational 5 1-8

Carotid Sinus 1 0-4

Orthostatic hypotension 8 4-10

Medications 3 1-7

Psychiatric 2 1-7

Neurological 10 3-32

Organic Heart Disease 4 1-8

Cardiac Arrhythmias 14 4-38

Unknown 34 13-41

Causes of Syncope1

1Kapoor W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc: 1998; 1-13.

Syncope: Etiology

Orthostatic CardiacArrhythmia

StructuralCardio-

Pulmonary

*

1• Vasovagal• Carotid

Sinus• Situational

CoughPost- micturition

2• Drug Induced• ANS

FailurePrimarySecondary

3• Brady

Sick sinusAV block

• TachyVTSVT

• Long QT Syndrome

4 • Aortic

Stenosis• HOCM• PulmonaryHypertension

5• Psychogenic• Metabolic

e.g. hyper-ventilation

• Neurological

Non-Cardio-

vascularNeurally-Mediated

Unknown Cause = 34%

24% 11% 14% 4% 12%

DG Benditt, UM Cardiac Arrhythmia Center

Causes of Syncope-like States

Migraine* Acute hypoxemia* Hyperventilation* Somatization disorder (psychogenic syncope) Acute Intoxication (e.g., alcohol) Seizures Hypoglycemia Sleep disorders

* may cause ‘true’ syncope

Section III:

Diagnosis and Evaluation Options

Syncope Diagnostic Objectives

Distinguish ‘True’ Syncope from other ‘Loss of Consciousness’ spells:SeizuresPsychiatric disturbances

Establish the cause of syncope with sufficient certainty to:Assess prognosis confidentlyInitiate effective preventive treatment

Initial Evaluation(Clinic/Emergency Dept.)

Detailed history Physical examination 12-lead ECG Echocardiogram (as available)

Syncope Basic Diagnostic Steps

Detailed History & PhysicalDocument details of eventsAssess frequency, severityObtain careful family history

Heart disease present? Physical examECG: long QT, WPW, conduction system diseaseEcho: LV function, valve status, HOCM

Follow a diagnostic plan...

Conventional Diagnostic Methods/YieldTest/Procedure Yield

(based 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 14 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, 19926 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.

Syncope Evaluation and Differential Diagnosis

Complete DescriptionFrom patient and observers

Type of Onset Duration of Attacks Posture Associated Symptoms Sequelae

History – What to Look for

12-Lead ECG

Normal or Abnormal?Acute MISevere Sinus Bradycardia/pauseAV BlockTachyarrhythmia (SVT, VT)Preexcitation (WPW), Long QT, Brugada

Short sampling window (approx. 12 sec)

Carotid Sinus Massage

Site: Carotid arterial pulse just below thyroid cartilage

Method:Right followed by left, pause betweenMassage, NOT occlusionDuration: 5-10 secPosture – supine & erect

Carotid Sinus Massage

Outcome: 3 sec asystole and/or 50 mmHg fall in systolic blood

pressure with reproduction of symptoms =

Carotid Sinus Syndrome (CSS) Contraindications

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

Risks1 in 5000 massages complicated by TIA

Conventional AECG

Low Yield, Poor Symptom / Arrhythmia Concordance*

8 studies, 2612 patients19% pts had symptoms with AECG

Only 4% had arrhythmia with symptoms

79% pts were without symptoms14% had arrhythmia despite absence of

symptoms

* ACC/AHA Task Force, JACC 1999;912-948

Method CommentsHolter (24-48 hours) Useful for infrequent events

Event Recorder Useful for infrequent eventsLimited value in sudden LOC

Loop Recorder Useful for infrequent eventsImplantable type more convenient (ILR)

Wireless (internet) Event Monitoring

In development

Ambulatory ECG

Head-up Tilt Test (HUT)

Unmasks VVS susceptibility

Reproduces symptoms Patient learns VVS

warning symptoms Physician is better able

to give prognostic / treatment advice

Head-Up Tilt Test (HUT)


Electroencephalogram

Not a first line of testingSyncope from SeizuresAbnormal in the interval

between two attacks – EpilepsyNormal – Syncope

Value of Event

Recorder in

Syncope

Linzer M. Am J Cardiol. 1990;66:214-219.

*Asterisk denotes event marker

Patient Activator Reveal® Plus ILR 9790 Programmer

Reveal® Plus Insertable Loop Recorder

ILR Recordings*56 yo woman with syncope accompanied with seizures.Infra-Hisian AV Block: Dual chamber pacemaker

65 yo man with syncope accompanied with brief retrograde amnesia.VT and VF: ICD and meds

*Medtronic data on file

Randomized Assessment of Syncope Trial

Usual care including:External loop recorderTilt test, EPS and others

Unexplained Syncopeafter history, physical exam, ECG, Holter

Low Risk (EF > 35%)

ILR

Diagnosis

+

+ --

ILR

External loop recorderTilt test, EPS, others

Krahn A, Klein GJ, Skanes Y. Circulation 2001; 104:46-51.

RAST Methods Prospective randomized trial

60 patients with unexplained syncope referred for cardiac investigation

Inclusion:Recurrent unexplained syncopeReferred to the arrhythmia service for cardiac investigationNo clinical diagnosis after history, physical, ECG and at least 24

hours of cardiac monitoring

Exclusion:LVEF < 35%Unable to give informed consentMajor morbidity precluding one year of follow-up


RAST Results

Unexplained Syncope

n=60

ILR

n=30

Conventional

n=30

In Follow-up

n=3

Diagnosed

n=14

Undiagnosed

n=13

Diagnosed

n=6

Undiagnosed

n=24


RAST Crossover Results


Unexplained Syncope

n=60

13/30

Undiagnosed after monitoring

6 accepted crossover to conventional

24/30

Undiagnosed after conventional

21 accepted crossover to ILR

Diagnosed

n=1

Undiagnosed

n=5

Diagnosed

n=8Undiagnosed

n=5

In follow-up

n=8

RAST - Diagnoses

0

2

4

6

8

10

12

14

Bradycardia Tachycardia Vasovagal Seizures

ILR Conventional

num

ber o

f pat

ient

s


Conventional EP Testing in Syncope

Limited utility in syncope evaluation

Most useful in patients with structural heart diseaseHeart disease……..50-80%No Heart disease…18-50%

Relatively ineffective for assessing bradyarrhythmias

Brignole M, Alboni P, Benditt DG, et al. Eur Heart Journal 2001; 22: 1256-1306.

EP Testing in Syncope:Useful Diagnostic Observations

Inducible monomorphic VT SNRT > 3000 ms or CSRT > 600 ms Inducible SVT with hypotension HV interval ≥ 100 ms (especially in

absence of inducible VT) Pacing induced infra-nodal block

Objectives:• Understand the mechanism of syncope in tilt-positive and tilt-

negative (isolated) patients

• Use the ILR to assess the correlation of rhythms captured during tilt testing and spontaneous recurrent episodes

Inclusion Criteria:• Patients with three or more syncopal episodes in the last 2

years

• Groups matched in age, sex, history of syncope, ECG, Echo abnormalities, SHD and arrhythmias

ISSUE StudyInternational Study of Syncope of Uncertain Etiology

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

ISSUE Study Design

Multicenter, prospective

111 syncope patients3 episodes in 2 years, first and last episode >6 months apart

History, physical exam, ECG, CSM, echo, Holter (24 hr), other tests as appropriate

Tilt test followed by implant of Reveal Insertable Loop Recorder

Follow-up to recurrent spontaneous episodeMoya A. Circulation. 2001; 104:1261-1267

ISSUE Study Results

Results

Tilt-Negative Syncope (Isolated)

n=82

Tilt-Positive Syncope

n=29

Recurrent Event Occurrence (#) 34% (28) 34% (10)

Mean Time to Recurrent Event

(range)

105 days (47-226) 59 (22-98)

ILR ECG Documented (#) 29% (24) 28% (8)Tachyarrhythmia 2% (2)Bradycardia 16% (13) 21% (6)

–Sinus Brady 2% (2) 3% (1)–Sinus Arrest 12% (10) 17% (5)–AV Block 1% (1)

Total Arrhythmic 18% (15) 21% (6)

Normal Sinus Rhythm 11% (9) 7% (2)


ISSUE Study Conclusions:

• Homogeneous findings from tilt-negative and tilt-positive syncope patients were observed (clinical characteristics and outcomes). Most frequent finding was asystole secondary to progressive sinus bradycardia, suggesting a neuromediated origin

• In this study tilt-negative patients had as many arrhythmias (18%) as tilt-positive patients (21%)

• In tilt-positive patients the spontaneous episode ECG was more frequently asystolic than what was predicted by tilt test


ISSUE Study Implications HUT outcome was not predictive of

vasodepressor vs. cardioinhibitory responseBradycardia 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 postponing treatment until a spontaneous episode can be documented


Symptom-Rhythm Correlation

Auto Activation Point

Patient Activation Point

Diagnostic Limitations

Difficult to correlate spontaneous events and laboratory findings

Often must settle for an attributable cause

Unknowns remain 20-30% 1

1Kapoor W. In Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk NY; Futura Publishing Co, Inc: 1998; 1-13.

Unexplained Syncope DiagnosisHistory and Physical Exam

Surface ECG

Neurological Testing

• Head CT Scan• Carotid Doppler• MRI• Skull Films• Brain Scan• EEG

CV Syncope Workup

• Holter• ELR or ILR• Tilt Table• Echo

• EPS

Other CV Testing

• Angiogram• Exercise Test• SAECG

Psychological Evaluation

ENT Evaluation Endocrine Evaluation

Adapted from: W.Kapoor.An overview of the evaluation and management of syncope. From Grubb B, Olshansky B (eds) Syncope: Mechanisms and Management. Armonk, NY: Futura Publishing Co., Inc.1998.

Typical Cardiovascular Diagnostic Pathway

History and Physical, ECG

Syncope

KnownSHD

NoSHD

Echo

EPS

+

Treat

> 30 days; > 2 Events

Tilt ILR

Tilt Holter/ ELR

ILR

Tilt/ILR

< 30 days

-

Adapted from:Linzer M, et al. Annals of Int Med, 1997. 127:76-86.Syncope: Mechanisms and Management. Grubb B, Olshansky B (eds) Futura Publishing 1999Zimetbaum P, Josephson M. Annals of Int Med, 1999. 130:848-856.Krahn A et al. ACC Current Journal Review,1999. Jan/Feb:80-84.

Section IV:

Specific Conditions

Neurally-Mediated Reflex Syncope (NMS)

Vasovagal syncope (VVS) Carotid sinus syndrome (CSS) Situational syncope

post-micturitioncoughswallow defecationblood drawingetc.

NM Reflex Syncope: Pathophysiology

Multiple triggers Variable

contribution of vasodilatation and bradycardia

NMS – Basic Pathophysiology

CerebralCortex

VascularBed Bradycardia/

Hypotension

Baro-receptors

Heart

Feedback viaCarotid Baroreceptors

Other Mechanoreceptors

Parasympathetic (+)

sympathetic (+) ¯ Heart Rate¯ AV Conduction

_ Vasodilatation

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

Neurally Mediated Physiologic Reflex Mechanism with two Components:

Cardioinhibitory ( HR )Vasodepressor ( BP )

Both components are usually present

Vasovagal Syncope (VVS):Clinical Pathophysiology

Prevalence of VVS

Prevalence is poorly known Various studies report 8% to 37% (mean 18%)

of cases of syncope (Linzer 1997)

In general: VVS patients younger than CSS patients Ages range from adolescence to elderly

(median 43 years) Pallor, nausea, sweating, palpitations are common Amnesia for warning symptoms in older patients


16.3sec

Continuous Tracing1 sec

Spontaneous VVS

Management Strategies for VVS

Optimal management strategies for VVS are a source of debate Patient education, reassurance, instruction Fluids, salt, diet Tilt Training Support hose

Drug therapies Pacing

Class II indication for VVS patients with positive HUT and cardioinhibitory or mixed reflex

VVS: Tilt-Training

ObjectivesEnhance Orthostatic ToleranceDiminish Excessive Autonomic Reflex

ActivityReduce Syncope Susceptibility /

Recurrences

Technique Prescribed Periods of Upright PostureProgressive Increased Duration

Carotid Sinus Syndrome (CSS)

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

Etiology of CSS

Sensory nerve endings in the carotid sinus walls respond to deformation

“Deafferentation” of neck muscles may contribute

Increased afferent signals to brain stem

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

Carotid Sinus

Carotid Sinus Hypersensitivity(CSH)

Abnormal response to CSM Absence of symptoms attributable to CSS CSH reported frequent in ‘fallers’ (Kenny)

CSH CSS

CSS and Falls in the Elderly

30% of people >65 yrs of age fall each year1

Total is 9,000,000 people in USAApproximately 10% of falls in elderly persons are due to

syncope2

50% of fallers have documented recurrence3

Prevalence of CSS among frequent and unexplained fallers unknown but…CSH present in 23% of >50 yrs fallers presenting at ER 3

1Falling in the Elderly: U.S. Prevalence Data. Journal of the American Geriatric Society, 1995.2 Campbell et al: Age and Aging 1981;10:264-270.3Richardson DA, Bexton RS, et al. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the Accident and Emergency Department with “unexplained” or “recurrent” falls. PACE 1997

Section V:

Treatment Options

VVS: Pharmacologic Rx Salt /Volume

Salt tablets, ‘sport’ drinks, fludrocortisone

Beta-adrenergic blockers1 positive controlled trial (atenolol), 1 on-going RCT (POST)

Disopyramide SSRIs

1 controlled trial

Vasoconstrictors (e.g., midodrine)1 negative controlled trial (etilephrine)

Midodrine for Neurocardiogenic Syncope

Journal of Cardiovascular Electrophysiology Vol. 12, No. 8, Perez-Lugones, et al.

Months

p < 0.001Sym

ptom

– F

ree

Inte

rval

180160140120100806040200

100

80

60

40

20

0

FluidMidodrine

Status of Pacing in VVS

Perception of pacing for VVS changing: VVS with +HUT and cardioinhibitory response a Class IIb

indication1

Recent clinical studies demonstrated benefits of pacing in select VVS patients: VPS I VASIS SYDIT VPS II –Phase I ROME VVS Trial

1Gregoratos G, et al. ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmic Devices. Circulation. 1998; 97: 1325-1335.

Status of Pacing in VVS

Benefits of specific device features evolving:Some success with DDD/DDI hysteresis 1

• “False positives” may result in prolonged high rate intervention• Tied to lower rate intervention

Rate drop therapies designed for treating VVS syncope appear to be successful 2-4

1 Sutton R, et al. Circulation. 2000; 102:294-299.2 Connolly S, et al. J Am Coll Cardiol 1999; 33:16-20.3 Ammirati F, et al. Circulation. 2002; 104: 52-57.4 Ammirati F, et al. NASPE Abstract #307. PACE, Vol. 24, April 2002, Part II.

VPS-IVasovagal Pacemaker Study I

Connolly S, et al. J Am Coll Cardiol 1999; 33: 16-20.

Study Design:54 patients randomized, prospective, single center

_ 27 DDD pacemaker with rate drop response (RDR)_ 27 no pacemaker

Patient Inclusion Criteria:6 syncopal events ever+HUTRelative bradycardia*

*a trough heart rate <60/min if no isoproterenol used, <70/min if up to 2 mcg/min isoproterenol used, or <80/min if over 2 mcg/min isoproterenol used

VPS- I


Endpoints:Time to first syncope

Outcome:

RESULTS

PACEMAKER(n= 27)

CONTROL(n=27)

Number of patients w/syncopal recurrence 6 (22%) 19 (70%)

Mean time to first recurrence (days) 112 54

Relative risk reduction of syncope* 85.4% -*2p = 0.000022

VPS- I


CumulativeRisk(%)

100

90

80

70

60

50

40

30

20

10

015129630

Control (No Pacemaker)

2P=0.000022

Pacemaker

Time in Months

NumberAt Risk

C 27 9 4 2 1 0P 27 21 17 12 11 8

VPS-I

Conclusion:Dual-chamber pacing with rate drop responsereduces the likelihood of syncope in patientswith recurrent VVS.


VASIS Vasovagal Syncope International Study

Sutton, R, et al. Circulation. 2000; 102:294-299.

Study Design:42 patients, randomized, prospective, multicenter

_ 19 DDI pacemaker (80 bpm) with rate hysteresis (45 bpm)_ 23 no pacemaker

Patient Inclusion Criteria:> 3 syncopal events in 2 years and last event occurring within

6 months of enrollment and,Positive VASIS type 2A or 2B cardioinhibitory response to HUT

and,Age > 40 years or drug refractory if < 40 years

VASIS


Outcome:

RESULTS Pacemaker(n= 19)

No Pacemaker

(n=23)


Median time to first recurrence (months)* 15 5

*P= 0.0006

Endpoints:Time to first syncope

VASIS

Pacemaker

No-Pacemaker

p=0.0004

Years

% s

ynco

pe-fr

ee

100

80

60

40

20

0 2 3 4 5 6

7121415233140# of pts


VASIS

Conclusion:Dual-chamber pacing (at a rate of 80 bpm ) with rate hysteresis reduces the likelihood of syncope in patients with tilt-positive, cardioinhibitory syncope.


SYDIT Syncope Diagnosis and Treatment Study

Study Design:93 patients randomized, prospective, multicenter

_ 46 DDD pacemaker with rate drop response (RDR)_ 47 Atenolol 100 MG/D

Patient Inclusion Criteria: > 55 yrs> 3 syncopal episodes in 2 years + HUT with relative bradycardia (trough HR <60 bpm)

Ammirati F, et al. Circulation. 2001; 104:52-57.

SYDIT

Endpoints: Time to first syncope

Outcome:

RESULTS

PACED(n= 46)

DRUG(n= 47)

Number of patients w/syncopal recurrence* 2 (4%) 12 (25%)

Median time to first recurrence (days) 390 135

*P=0.004

Ammirati, et al. Circulation. 2001; 104:52-57.

Syncope-free Survival: Intention-to-Treat (n=46/paced, 47/drug).


SYDIT

1.0

Time (days)

100

0.9

0.8

0.7

0.6200 300 400 500 600 700 800 900 10000

P = 0.0032

drugpacemaker

% o

f syn

cope

free

pts

SYDIT

Conclusion:Dual-chamber pacing + RDR is superior to Atenolol in prevention of recurrent syncope in highly symptomatic patients with relative bradycardia during tilt-induced syncope.


VPS-II: Phase IVasovagal Pacemaker Study-II

Study Design:100 patients, randomized, prospective, multicenter

_ 50 DDD pacemaker with rate drop response (RDR)_ 50 ODO pacemaker (inactive mode)

Patient Inclusion Criteria:> 6 syncope events ever or > 3 syncope events in

2 years or > 1 syncope event in 6 months and,Positive HUT with syncope or presyncope and a

heart rate blood pressure product <9000

Presented at the 23rd Annual Scientific Sessions of the North American Society of Pacing and Electrophysiology. Late Breaking Clinical Trials, May 11, 2002.

VPS-II: Phase I

Endpoints: Time to first syncope

Outcome:

RESULTS

DDD Pacemaker(n= 50)

ODO Pacemaker(n= 50)


Relative Risk Reduction* 28.7% -

*P=0.153


0.4

0.3

0.2

ODODDD

P = 0.153 (one-sided)

Number at Risk ODO 40 37 35 32 31 21DDD 39 36 34 33 33 17

0 1 2 3 4 5 6

0.1

0.0

Cum

ulat

ive

Ris

k of

Sy

ncop

e


VPS-II: Phase I

VPS-II: Phase I

Conclusions: Lower than anticipated syncope event rate in the

control arm. Higher than anticipated event rate in the treatment

group. Consequence: treatment effect was less than VPS-I. Results favored pacing but the treatment effect was

not statistically significant.


VVS Pacing Trials Conclusions

DDD pacing reduces the risk of syncope

in patients with recurrent, refractory,

highly-symptomatic, cardioinhibitory

vasovagal syncope.

SAFE PACE Study Design

Randomized controlled trial (N=175): Pacing (87) vs. No Pacing (88)

Single center: Royal Victoria Infirmary, Newcastle, UK

Recruitment began: April 1998 12 month follow-up per patient Study concluded: May 2000

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

SAFE PACE Inclusion Criteria

Consecutive adults attending accident and emergency department• > 50 Years

- Experienced non-accidental fall

•Positive response to CSM


SAFE PACE Screening ProcessAccident and Emergency Attendees > 50 Yrs

Falls or Syncope

Non-accidental Fall

CSM Performed

Cardioinhibitory or Mixed CSH

RCT

Control Pacemaker


SAFE PACE Screening Results

RCT (n=175)

Control (n=88)

Pacemaker (n=87)

• No pacing intervention • Medtronic Thera DR(Rate Drop ResponseAlgorithm)


SAFE PACE ResultsNumber of Falls

Control

n=87

Pacemaker

n=84% Participants w/Falls

60% 58%

Total Number of Falls*

699 216

Mean Number of Falls**

9.3 4.1

* Falls during 12 months post randomization** Crude adjustment calculation


70%Reduction[OR 0.42; 95%CI: 0.23, 0.75]

Control

N=87

Pacemaker

N=84

% Participants w/Syncopal Events

22% 11%

Total Number of Syncopal Events

47 22

Mean Number Syncopal Events

1.14 0.20

SAFE PACE ResultsNumber of Syncopal Episodes

50%Reduction[OR 0.53; 95%

CI 0.23; 1.20 ns]

* Syncopal events 12 months past randomization** Crude adjustment calculation


Control

n= 87

Pacemaker

n= 84

% Participants w/Injurious Events

41% 35%

Total Number Injury Events

202 61

-Fractures

-Soft Tissue Injury

4

198

3

58

SAFE PACE ResultsNumber of Injury Events

70%Reduction

* Injurious events 12 months post randomization


SAFE PACE Conclusions

In patients with unexplained falls and a diagnosis of Cardioinhibitory CSH, cardiacpacing reduced the total number of:

Falls by 70% Syncopal events by 53% Injurious events by 70%


Role of Pacing in CSS --Syncope Recurrence Rate

Brignole et. Al. Diagnosis, natural history and treatment. Eur JCPE. 1992; 4:247-254

0%

25%

50%

75%

No Pacing Pacing

57%

%6% R

ecur

renc

e

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)

Section VI:

Insights into More Efficient and Effective Diagnosis and Treatment

Principal Causes of Orthostatic Syncope

Drug-induced (very common) diuretics vasodilators

Primary autonomic failure multiple system atrophy Parkinsonism

Secondary autonomic failure diabetes alcohol amyloid

Alcohol orthostatic intolerance apart from neuropathy

Syncope Due to Arrhythmia or Structural CV Disease:

General Rules

Often life-threatening and/or exposes patient to high risk of injury

May be warning of critical CV disease Aortic stenosis, Myocardial ischemia, Pulmonary

hypertension

Assess culprit arrhythmia / structural abnormality aggressively

Initiate treatment promptly

Principal Causes of Syncope due to Structural Cardiovascular Disease

Acute MI / IschemiaAcquired coronary artery disease Congenital coronary artery anomalies

HOCM Acute aortic dissection Pericardial disease / tamponade Pulmonary embolus / pulmonary

hypertension Valvular abnormalities

Aortic stenosis, Atrial myxoma

Syncope Due to Cardiac Arrhythmias

Bradyarrhythmias Sinus arrest, exit block High grade or acute complete AV block

Tachyarrhythmias Atrial fibrillation / flutter with rapid ventricular

rate (e.g. WPW syndrome) Paroxysmal SVT or VT Torsades de pointes

Rhythms During Recurrent Syncope

Krahn A, et al. Circulation. 1999; 99: 406-410

Normal Sinus Rhythm

58%Normal Sinus Rhythm

58%

Bradycardia

36%

Tachyarrhythmia

6%

AECG: 74 yr Male, Syncope

From the files of DG Benditt, UM Cardiac Arrhythmia Center

Syncope: Torsades


83 yo womanBradycardia: Pacemaker implanted

28 yo man in the ER multiple times after falls resulting in traumaVT: ablated and medicated

Reveal ® ILR recordings; Medtronic data on file.

Infra-His Block


Drug-Induced QT Prolongation Antiarrhythmics

Class IA ...Quinidine, Procainamide, DisopyramideClass III…Sotalol, Ibutilide, Dofetilide, Amiodarone, (NAPA)

Antianginal Agents (Bepridil)

Psychoactive AgentsPhenothiazines, Amitriptyline, Imipramine, Ziprasidone

AntibioticsErythromycin, Pentamidine, Fluconazole

Nonsedating antihistamines (Terfenadine), Astemizole

Others (Cisapride), Droperidol

Treatment of Syncope Due to Bradyarrhythmia

Class I indication for pacing using dual- chamber system wherever adequate atrial rhythm is available

Ventricular pacing in atrial fibrillation with slow ventricular response

Treatment of Syncope Due to Tachyarrhythmia

Atrial Tachyarrhythmias;AVRT due to accessory pathway – ablate pathwayAVNRT – ablate AV nodal slow pathwayAtrial fib– Pacing, linear / focal ablation, ICD selected ptsAtrial flutter – Ablation of reentrant circuit

Ventricular Tachyarrhythmias;Ventricular tachycardia – ICD or ablation where appropriateTorsades de Pointes – withdraw offending Rx or ICD (long-

QT/Brugada)

Drug therapy may be an alternative in many cases

Conclusion

Syncope is a common symptom, often with dramatic consequences,

which deserves thorough investigation and appropriate treatment of its cause.

DisclaimerINDICATIONS9526 Reveal® Plus Insertable Loop RecorderThe Reveal Plus Insertable Loop Recorder (ILR) is an implantable patient activated monitoring system that records subcutaneous ECG and is indicated for patients who experience transient symptoms that may suggest a cardiac arrhythmia. 9790 ProgrammerThe Medtronic 9790 Programmers are portable, microprocessor based instruments used to program Medtronic implantable devices. 6191 ActivatorThe Model 6191 Activator is intended for use in combination with a Medtronic Model 9525 Reveal ® and the Model 9526 Reveal Plus Insertable Loop Recorders. CONTRAINDICATIONSThere 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/PRECAUTIONS9526 Reveal Plus Insertable Loop RecorderPatients 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 ActivatorOperation 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. See the appropriate technical manual for detailed information regarding indications, contraindications, warnings, and precautions. Caution: Federal law (U.S.A.) restricts this device to sale by or on the order of a physician.

DisclaimerINDICATIONS

Medtronic.Kappa 700 Series Pacemakers

The Medtronic.Kappa 700 Series pacemakers are indicated for rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity and are also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of AV synchrony. Dual chamber modes are specifically indicated for treatment of conduction disorders that require restoration of both rate and AV synchrony, which include various degrees of AV block to maintain the atrial contribution to cardiac output and VVI intolerance (e.g., pacemaker syndrome) in the presence of persistent sinus rhythm.

9790 Programmer

The Medtronic 9790 Programmers are portable, microprocessor based instruments used to program Medtronic implantable devices.

9462

The Model 9462 Remote Assistant is intended for use in combination with a Medtronic implantable pacemaker with Remote Assistant diagnostic capabilities.

CONTRAINDICATIONS

The Medtronic.Kappa 700 Series pacemakers are contraindicated for the following applications:

· Dual chamber atrial pacing in patients with chronic refractory atrial tachyarrhythmias.

· Asynchronous pacing in the presence (or likelihood) of competitive paced and intrinsic rhythms.

· Unipolar pacing for patients with an implanted cardioverter-defibrillator (ICD) because it may cause unwanted delivery or inhibition of ICD therapy.

WARNINGS/PRECAUTIONS

Medtronic.Kappa 700 Series patients 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, inappropriate sensing and/or therapy.

See the appropriate technical manual for detailed information regarding indications, contraindications, warnings, and precautions.

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

Additional Slides

Falls -- Incidence, Recurrence, CHS*

1 Falling in the Elderly, 1995.2 Richardson, PACE, 1997.

0%

25%

50%

75%

Incidence> 65 yrs. old

Recurrence CSH* presentin fallers > 50 yrs.presenting at ER

30% 1

50% 1

23% 2

Per

cent

of P

eopl

e

* Carotid Sinus Hypersensitivity

VVS Pacing TrialsComparison Summary

Pacing in VVS

Two randomized, controlled trials suggest benefit in selected patients with multiple (>5 lifetime) syncope recurrences and one or more of: prominent cardioinhibitory featuresasystolic pause >10 secondssustained HR<40/minute

VVS Recurrences

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

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

Sheldon et al. Circulation 1996; 93: 973-81.

Savage et al. STROKE 1985; 16: 626-29.

SAFE PACE 2: Syncope and Falls in the Elderly

30% of individuals >65 yrs fall each year 5% of falls result in fractures 1% of falls result in hip fractures SAFEPACE Pilot Study

18% prevalence of CSH in unexplained ‘fallers’

31% in ‘fallers’ >80 yrs Kenny RA, J Am Coll Cardiol 2001; 38:1491-1496.

Both

Rate Drop Response Overview

Detection Options

DropDetect

Low RateDetect

Detects relative heart rate drops

of a pre-determined size

Detects heart rate that falls to a user-defined

lower rate

Detection occurs when either Drop Detection or Low

Rate Detection criteria are met

Rate Drop Detection in Medtronic Kappa® Series Pacemakers

Drop Detection with Intervention

Drop Detection Method: Drop Size 25, Drop Rate 70

40

50

60

70

80

90

100

110

Ven

tricu

lar R

ate

Drop Size=25 bpm

Drop Rate

Peak Rate=90 bpm

2 consecutive beats < Drop Size and Drop Rate


Drop Detect Peak Rate

Drop Detection Method: Drop Size 25

40

50

60

70

80

90

100

110

120

Ven

tricu

lar R

ate

Drop Size=25 bpm

Peak Rate=90 bpm


Low Rate Detection Method: Lower Rate 40, Detection beats 2

30

40

50

60

70

80

90

100

110

Ven

tricu

lar R

ate

Lower Rate

2 consecutive paced beats at Lower Rate

Low Rate Detect


Using Both Detection Algorithms

When both detection algorithms are used:Detection occurs when either Drop Detection

or Low Rate Detection criteria are metIntervention Rate, Duration and Termination

are programmed the same as when using the individual detection modes


Rate Drop Intervention Therapy

DDD or DDI pacing Pacing intervention

Paces at programmed Intervention Rate for programmed duration

Pacing terminationPacing rate decreases until there are three

consecutive atrial senses or Lower Rate is reached


Challenges of Syncope Cost

Cost/year Cost/diagnosis

Quality of Life Implications Work/financial Mobility (automobiles) Psychological

Diagnosis & Treatment Diagnostic yield and repeatability of tests Frequency and clustering of events Difficulty in managing/treating/controlling future events Appropriate risk stratification Complex Etiology

Diagnosing VVS

Patient history and physical exam Positive tilt table test

(ACC Consensus Protocol) Overnight fast ECG Blood pressure Supine and upright Tilt to 60-80 degrees Isoproterenol Re-tilt

DG Benditt, Tilt Table Testing, 1996.

60° - 80°

VVS: Treatment Overview Education

symptom recognition reassurancesituation avoidance

Tilt-Training prescribed upright posture

Pharmacologic Agentssalt/volume management beta-adrenergic blockersSSRIsvasoconstrictors (e.g., midodrine)

Cardiac Pacemakers

Tilt-Training: Clinical Outcomes

42 HUT positive (21±13 min) VVS patients Home training: two 30 minute sessions daily Outcomes

41/42 pts --->45 min asymptomatic HUT Clinical follow-up: 15.1±7.8 mos

• 36 pts syncope free• 4 pts: presyncope• 1 pt: syncope recurrences

Reybrouck et al. PACE 2000; 23:493-8

SyncopeDxTxStrategy[1]

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