www.gimsi.it

Corso Avanzato GIMSI sulla Sincope

Il nuovo ruolo del tilt test

Michele BrignoleCentro Aritmologico &

Syncope Unit - Lavagna

Tilt table testing: limitations

• Too often negative in pts with likely VVS (“low sensitivity”)

• Too often positive in pts without VVS syncope (“low specificity”)

• No value in assessing efficacy of treatment with drugs or pacemaker

Someone stopped to perfom it (“clinical history better than tilt table testing”)

Tilttesting:positivityrate

92% Typical VVS,emotional trigger(Clom)78% Typical VVS, situational trigger(TNT)73%-65% Typical VVS,miscellaneous (Clom) (TNT)

56%-51% Likely reflex, atypical (TNT)47% Cardiac syncope (TNT)45% Likely tachyarrhythmic syncope (Passive)36%-30% Unexplained syncope (TNT) (Clom)

13%-8% Subjects withoutsyncope(Passive) (Clom) (TNT)8

Sutton & Brignole. Eur Heart J 2014; 35: 2211-12

A positive tilt test suggests the presence of a hypotensive susceptibility, which plays a role in causing syncope irrespective of the etiology and mechanism of syncope.

Changed indications for Tilt Table Testing

Old (initial)indications Newindications

Diagnosis of VVS Susceptibilityto orthostaticstress,irrespective of theetiology of syncope

Sutton & Brignole. Eur Heart J 2014; 35: 2211-12

ISSUE 3

SYNCOPE

Ptsaffectedbysevere,recurrentreflexsyncopes,aged>40yrs

ILRimplantation(RevealDX/XT)

ILRfollow-up(max2yrs)

ILRscreeningphase

ISSUE3therapyphase

TiltTableTesting(Passive+TNT)

ILReligibilitycriteria:• Asystolic syncope≥3s,or• Non-syncopalasystole≥6s

R

Pm ON Pm OFF

Study design

0

.1

.2

.3

.4

.5

.6

.7

.8

.9

1

Free

dom

from

syn

copa

l rec

urre

nce

38 32 27 22 16 14 13 13 11Pm ON39 31 25 21 21 18 15 12 8Pm OFF

Number at risk

0 3 6 9 12 15 18 21 24Months

Kaplan-Meier survival estimates

log rank: p=0.039RRR at 2 yrs: 57%

Pm ON

Pm OFF

First syncope recurrence(intention-to-treat)

ISSUE 3

SYNCOPE

25%

37%

25%

57%

Brignole et al. Circulation 2012;125:2566-2571

Characteristics Recurrencen=9

No recurrence

n=43

P value

Tilt testing: positive 89% 42% 0.0004- Asystolic (Vasis 2B) 44% 23% ns- Non-asystolic 44% 19% ns

ILR findings (asystole)- Asystole duration, sec 9 8 ns- Type 1A (sinus arrest) 44% 63% ns- Type 1B (sinus brady + AV block) 33% 14% ns- Type 1C (AV blocK) 22% 24% ns

Systolic blood pressure- Supine, mmHg 135 130 ns- Standing, mmHg 127 118 ns

ISSUE 3

SYNCOPE

Factors predicting recurrence of syncope after pacemaker therapy (II)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

Free

dom

from

syn

copa

l rec

urre

nce

45 35 31 22 22 18 14 9NO THER26 19 19 15 11 10 9 9PM TT-26 14 10 9 8 6 4 3PM TT+

Number at risk

0 3 6 9 12 15 18 21Months

PM,TT+

PM,TT–

NoPM

ISSUE 3

SYNCOPE

SyncoperecurrenceafterPMtherapyaccordingtotilttestresults

5%vs55%at21monthslogrank:p=0.004

Brignole M et al. Circ Arrhythm Electrophysiol 2014;7:10-16

Am J Cardiol 1995; 76: 720

Non-CI forms

CI form

Negative or not performed

Recurrence of syncope according to tilt test results

Log rank: p=0.008

Solari D et al. Europace 2013

Pm, TT negative

Pm, TT Positive

No Pm, ILRLog rank for trend:p = 0.01

p = 0.03

p = n.s.

SyncopeUnitProject2(SUP2) SUP 2 study: 3-years extended follow-up

Europace 2016

Changed indications for Tilt Table Testing

Old (initial)indications Newindications

Diagnosis of VVS Susceptibilityto orthostaticstress,irrespective of theetiology of syncope

Identification of candidates forpermanent pacing (CI form)

Identification of non-responderto cardiac pacing (any positiveresponse)

Sutton & Brignole. Eur Heart J 2014

Reflex syncope: Dual-action model

Hypotensive susceptibility

YES (Tilt +)Low reflex threshold

NO (Tilt -)High reflex threshold

Trigger(neuro and/or humoral)

Vasovagal syncope(hypotension-bradycardia)

Cardio-inhibitoryreflex syncope

+ +++

Hypotension phenotype domain(pacing low responder)

Bradycardia phenotype domain(pacing high-responder)

Tilttabletesting:asystolicform(VASIS2B)

44% Typical emotional VVS (Clom)24% Typical emotional VVS (TNT)21% Likely reflex,notrigger(TNT)

17% Typical peripheral triggerVVS(Clom)10% Typical peripheral triggerVVS(TNT)

8% Unexplained syncope(Clom)7% Unexplained syncope (TNT)6% Subjects w/tsyncope (Passive)0% Cardiac syncope (TNT)0% Subjects w/tsyncope (TNT)

Sutton & Brignole. Eur Heart J 2014; 35: 2211-12

Tilttest+ ILR+

28

48

Asystole(Vasis2B)

MorVD(Vasis1,2A,3)

Asystole47

29 Slightrhythmvariations

24(86%)

4(14%)

23(48%)

25(52%)

Total76pts

Positivepredictive value of asystolictilt:0.86(95%CI 0.70-0.95)

ISSUE 3

SYNCOPE

CorrelationbetweentilttestresponsesandILR-documentedmechanism

Brignole M et al. Circ Arrhythm Electrophysiol 2014;7:10-16

Log rank for trend:p = 0.01

Pm-CSS

Pm-ILRPm-VASIS 2B

ILR

SyncopeUnitProject2(SUP2) SUP 2 study: 3-years extended follow-up

Europace 2016

18

Benefit of dual-chamber pacing with Closed Loop Stimulation (CLS) in tilt-induced cardio-inhibitory

reflex syncope.

A randomized double-blind parallel trial

BioSyncBioSync

M. Brignole (PI) - M. Tomaino (Co-PI)

Perform CSM & tilt table test

CI-CSS

VASIS 2B response

Type 1asystole

Implant an ILR

Severe, recurrent, unpredictable syncopes, age >40 yrs

Clinical features no Pacing not indicated

yes

Implant a DDD PM & counteract hypotensivesusceptibility

yes

no

Implant a DDD PMYes & Tilt negative

no

Pacing not indicated

Implant a DDD PM & counteract hypotensivesusceptibility

Yes & Tilt positive

Pacing for neurally-mediated syncope: decision tree

no

Implant a DDD PMYes & Tilt negative

Implant a DDD PM & counteract hypotensivesusceptibility

Yes & Tilt positive

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Italian Multidisciplinary Group for the Study of Syncope:

Established in 2003 by 5 national societies:- arrhythmology, - internal medicine, - emergency medicine, - geriatrics- neurology