Andrea Ungar, MD, PhD, FESC

Syncope Unit, Hypertension Centre Geriatric Cardiology and Medicine

University of Florence, Italy

Il tilt test: non piu’ test per la diagnosi, ma …………..

Il tilt test: per anni la nostra sicurezza

Mr. L.B., 93 year-old Two recent

unexplained syncope

Head-up tilt test potentiated with glyceryl trinitrate

1997

SIGG 2002 Simposio sincope multidisciplinare

0

25

50

75

100

Positive Esagerate Negative

Controlli (n=64)

p < 0.001

p < 0.01

(%)

0

25

50

75

100

Positive Esagerate Negative

Pazienti (n=324)

p < 0.05 (%

)

Tollerabilità, Specificità e Tasso di positività del Tilt Table Test potenziato con Nitroglicerina nel paziente anziano con

sincope di origine indeterminata

Anziani (age>65 yrs.) Giovani (age<65 yrs.) Del Rosso A, Ungar A et al, JAGS 50: 1324-1328, 2002

Head-up tilt test potenziato con nitroglicerina Syncope unit

Firenze 2014

Continuiamo

a fare tilt

Classe Indicazioni all’esecuzione del tilt test

Livello di evidenza

I

Sincope ricorrente in assenza di cardiopatia, o in presenza di cardiopatia quando è stata esclusa una causa cardiaca di sincope

C

I

Sincope isolata o rara in contesto ad alto rischio (trauma o attività lavorativa a rischio)

C

I

Quando può essere di valore clinico d imos t ra re a l paz ien te l a suscettibilità alla sincope vasovagale

C

ESC Guidelines 2009

Classe Indicazioni all’esecuzione del tilt test

Livello di evidenza

IIa P e r d i s c r i m i n a r e t r a s i n c o p e neuromediata e ipotensione ortostatica

C

IIb Per differenziare la sincope con movimenti mioclonici dall’epilessia

C

IIb Per valutare pazienti con cadute inspiegate ricorrenti

C

IIb Per valutare pazienti con sincope frequente e malattia psichiatrica

C

III Per valutare il trattamento B

ESC Guidelines 2009

Classificazione VASIS della risposta vasovagale durante tilt test (Brignole 2009)

•  Tipo 1 Mista •  Tipo 2 A Cardioinibitrice senza asistolia •  Tipo 2 B Cardioinibitrice con asistolia •  Tipo 3 Vasopressiva •  Eccezione 1 (incompetenza cronotropa) •  Eccezione 2 (eccessivo incremento

frequenza cardiaca)

Il tilt test: arrivano i dubbi

ISSUE 3"

SYNCOPE"

ISSUE 3 International Study on Syncope of Uncertain Etiology 3

Background

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

62 42 35 29 23 19 16 14PM86 63 57 46 44 35 30 22NO PM

Number at risk

0 3 6 9 12 15 18 21Months

27% vs 54% at 21 months log rank: p=0.01

RRR (hazard ratio) : 57% NNT: 3.7

PM (n=62)

No PM (n=86)

ISSUE 3"

SYNCOPE"

Pacemaker therapy vs no pacemaker therapy in established NMS patients

Recurrence of syncope

To compare the diagnosis of NMS made at initial evaluation and with TT with that obtained with the documentation of a spontaneous event made by implantable loop recorder (ILR)

Aim of the study

Ungar A. et al, heart 2013

! Patients ≥ 40 years old who had suffered ≥3 syncopal episodes of likely NeuroMediated Syncope (NMS) aetiology in the previous 2 years.

! NMS was defined as any form of reflex syncope, with the exception of carotid sinus syndrome, and a sufficiently severe clinical presentation to warrant specific treatment.

! NMS was considered likely when the clinical history was consistent with NMS and competing diagnoses were excluded.

Inclusion criteria

All these individuals received an ILR and were followed up.

Ungar A. et al, heart 2013

NMS at initial evaluation ILR implantation 504

Diagnosis after ECG documentation

Follow-up: 15±11 months

187 (37%)

Hypotensive NMS

63 (34%)

Asystolic NMS

99 (53%)

Intrinsic cardiac

arrhythmias 21 (11%)

Non-arrhythmic

T-LOC 4 (2%)

NMS likely 162 (87%)

NMS excluded 25 (13%)

ISSUE 3"

SYNCOPE"Diagnosis

Ungar A. et al, heart 2013

ISSUE 3"

SYNCOPE"Diagnosis

Intrinsic cardiac arrhythmias

21 (11%)

Non-arrhythmic T-LOC 4 (2%)

NMS excluded 25 (13%)

•  long pause post-tachyarrhythmia [#8] •  parox atrial fibrillation [#3] •  AVNRT [#3] •  persistent bradycardia [#3] •  ventricular tachycardia [#4]

•  non-syncopal T-LOC [#3], •  orthostatic hypotension [#1]

Ungar A. et al, heart 2013

Characteristics NMS n=162

Cardiac n=21

P value

Age, mean 64 68 ns Men 46% 62% ns Syncope events:

- Total events, median 8 5 ns - Events last 2 years, median 4 4 ns - Events last 2 years without prodrome, median 3 3 ns - Age at first syncope, mean 48 53 ns - Interval between first and last episode, median 9 5 ns - History of presyncope 55% 48% ns - Hospitalization for syncope 42% 57% ns - Injuries related to fainting: - Major (fractures, concussion) 11% 5% ns - Minor (bruises, contusion, hematoma) 44% 43% ns - Typical vasovagal/situational presentation 49% 43% ns - No prodromes 54% 67% ns

ISSUE 3"

SYNCOPE"Factors predicting intrinsic cardiac syncope (I)

Ungar A. et al, heart 2013

Characteristics NMS n=162

Cardiac n=21

P value

Tilt testing: performed 84% 81% ns - Positive of those performed 56% 47% ns Medical history - Structural heart disease 12% 10% ns - Atrial tachyarrhythmias 5% 38% 0.001 - Hypertension 50% 49% ns - Diabetes 11% 10% ns - Neurologiacal/psychiatric 4% 0% ns Echocardiogram - Any abnormality 8% 10% ns Concomitant medications - Anti-hypertensive 48% 29% ns - Psychiatric 12% 0% ns - Any other drugs 27% 33% ns

ISSUE 3"

SYNCOPE"Factors predicting intrinsic cardiac syncope (II)

Ungar A. et al, heart 2013

Tilt test + ILR +

28

48

Asystole (Vasis 2B)

M or VD (Vasis 1,2A,3)

Asystole 47

29 Slight rhythm variations

24(86%)

4 (14%)

23(48%)

25(52%)

Total 76 pts

Positive predictive value of asystolic tilt: 0.86 (95% CI 0.70-0.95)

ISSUE 3"

SYNCOPE"Correlation between tilt test responses and

ILR-documented mechanism

Ungar A. et al, heart 2013

ISSUE 3"

SYNCOPE" Conclusions •  A non-negligible risk of misdiagnosis exists when NMS is

diagnosed in patients >40 years according to clinical history, physical examination and exclusion of other competing causes even if strict standardised guideline-based diagnostic criteria are applied when comparison with ILR findings is made.

•  The accuracy of the diagnosis of NMS made on initial evaluation is 87%, but a small, though non-negligible, number of patients have a different diagnosis, especially an intrinsic arrhythmic cause

•  The study suggests a diagnosis different from the original one of NMS in TT was unable to discriminate between cardiac (non-NMS) and presumed NMS with the exception of an asystolic response which was highly specific.

•  These data are anticipated to move use of the ILR more towards being the ‘gold standard’ in diagnosis of presumed NMS from clinical assessment Ungar A. et al, heart 2013

ISSUE 3"

SYNCOPE" Conclusions

•  These patients are indistinguishable from true NMS patients on standard clinical evaluation and were potentially at risk of lifethreatening arrhythmias, which could be identified and treated only by means of an ILR strategy. This aspect may be relevant in clinical practice.

•  The use of TT in order to confirm the diagnosis is hampered by low sensitivity and specificity. An interesting original finding of this study is that an asystolic positive response (VASIS 2B) seems to have an excellent specificity even if to the detriment of sensitivity.

•  These data are anticipated to move use of the ILR more towards being the ‘gold standard’ in diagnosis of presumed NMS from clinical assessment Ungar A. et al, heart 2013

However, caution should be exercised before such therapy is offered to patients with a positive tilt test even if they have had an asystolic response during the test, and asystole has been documented during a spontaneous event (tilt-positive asystolic NMS).

Although some benefit may still be possible in terms of reduced syncopal burden, patients should be informed that they will likely have some recurrence of syncope, despite cardiac pacing.

Finally, tilt test should no longer be regarded as a test aimed at the diagnosis of NMS, but rather as a useful tool for risk stratification for pacemaker therapy

Le risposte atipiche al tilt ... Una risorsa

Pre-syncopal phase

Syncopal phase

TNG S

HR

BP

150

110

70

30

70

110

1min

Dysautonomic vasovagal syncope pattern

Brignole, Europace 2002

Il tilt test nelle

TPdC non sincopali

Take Home Message

1.  Nella sincope vasovagale classica il ruolo del Tilt Test «sta cambiando»: dalla diagnosi alla terapia ed alla stratificazione prognostica

2.  La sincope «cardioinibitoria» al tilt è sempre più un «rebus» per i medici che si occupano di sincope (predice la sincope asistolica spontanea ma recidiva di più quando impianto un pace-maker)

3.  Il Tilt test è uno strumento utile per la diagnosi di forme neuromediate «peculiari»

4.  Il Tilt test è utile per «smascherare» la sincope in forme di TPdC non ben definite ed apparentemente non sincopali

Grazie per la vostra attenzione

Grazie per la vostra attenzione