Il tilt test: non piu test per la diagnosi, ma.. Andrea Ungar, MD, PhD, FESC

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Gustavo Romano
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1 Il tilt test: non piu test per la diagnosi, ma.. Andrea Ungar, MD, PhD, FESC Syncope Unit, Hypertension Centre Geriatric Cardiology and Medicine University of Florence, Italy

2 Il tilt test: per anni la nostra sicurezza

3 Mr. L.B., 93 year-old Two recent unexplained syncope Head-up tilt test potentiated with glyceryl trinitrate 1997

4 SIGG 2002 Simposio sincope multidisciplinare

5 Tollerabilità, Specificità e Tasso di positività del Tilt Table Test potenziato con Nitroglicerina nel paziente anziano con sincope di origine indeterminata 100 Controlli (n=64) p < Pazienti (n=324) (%) 50 (%) 50 p < p < Positive Negative Esagerate 0 Positive Negative Esagerate Anziani (age>65 yrs.) Giovani (age<65 yrs.) Del Rosso A, Ungar A et al, JAGS 50: , 2002

6 Head-up tilt test potenziato con nitroglicerina Syncope unit Firenze 2014 Continuiamo a fare tilt

7 Classe Indicazioni all esecuzione del tilt test I I I Sincope ricorrente in assenza di cardiopatia, o in presenza di cardiopatia quando è stata esclusa una causa cardiaca di sincope Sincope isolata o rara in contesto ad alto rischio (trauma o attività lavorativa a rischio) Quando può essere di valore clinico dimostrare al paziente la suscettibilità alla sincope vasovagale Livello di evidenza C C C ESC Guidelines 2009

8 Classe IIa IIb IIb IIb Indicazioni all esecuzione del tilt test Per discriminare tra sincope neuromediata e ipotensione ortostatica Per differenziare la sincope con movimenti mioclonici dall epilessia Per valutare pazienti con cadute inspiegate ricorrenti Per valutare pazienti con sincope frequente e malattia psichiatrica Livello di evidenza C C C C III Per valutare il trattamento B ESC Guidelines 2009

9 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)

10 Il tilt test: arrivano i dubbi

13 Background ISSUE 3" SYNCOPE" ISSUE 3 International Study on Syncope of Uncertain Etiology 3

14 SYNCOPE" ISSUE 3" Pacemaker therapy vs no pacemaker therapy in established NMS patients 1.00 Recurrence of syncope PM (n=62) No PM (n=86) % vs 54% at 21 months log rank: p=0.01 RRR (hazard ratio) : 57% NNT: Months Number at risk NO PM PM

16 Aim of the study 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) Ungar A. et al, heart 2013

17 Inclusion criteria! 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. All these individuals received an ILR and were followed up. Ungar A. et al, heart 2013

18 SYNCOPE" ISSUE 3" Diagnosis NMS at initial evaluation ILR implantation 504 Diagnosis after ECG documentation 187 (37%) Follow-up: 15±11 months NMS likely 162 (87%) NMS excluded 25 (13%) Asystolic NMS 99 (53%) Hypotensiv e NMS 63 (34%) Intrinsic cardiac arrhythmias 21 (11%) Nonarrhythmic T-LOC 4 (2%) Ungar A. et al, heart 2013

19 SYNCOPE" ISSUE 3" Diagnosis NMS excluded 25 (13%) Intrinsic cardiac arrhythmias 21 (11%) Non-arrhythmic T-LOC 4 (2%) 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

$first and last episode, median 9 5 ns - History of presyncope 55% 48% ns - Hospitalization for syncope 42% 57% ns - Injuries related to fainting: - Major (fractures,$

20 SYNCOPE" ISSUE 3" Ungar A. et al, heart 2013 Factors predicting intrinsic cardiac syncope (I) Characteristics NMS n=162 Cardiac n=21 P value Age, mean 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 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

21 SYNCOPE" ISSUE 3" Ungar A. et al, heart 2013 Factors predicting intrinsic cardiac syncope (II) 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% 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

22 SYNCOPE" ISSUE 3" Ungar A. et al, heart 2013 Correlation between tilt test responses and ILR-documented mechanism Tilt test + Total 76 ILR + pts Asystole (Vasis 2B) 28 24(86%) 4 (14%) 47 Asystole 23(48%) M or VD (Vasis 1,2A,3) 48 25(52%) 29 Slight rhythm variations Positive predictive value of asystolic tilt: 0.86 (95% CI )

23 SYNCOPE" ISSUE 3" 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

24 SYNCOPE" ISSUE 3" 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

28 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

29 Le risposte atipiche al tilt... Una risorsa

30 Dysautonomic vasovagal syncope pattern Pre-syncopal phase Syncopal phase HR BP min Brignole, Europace 2002 TNG S

31 Il tilt test nelle TPdC non sincopali

37 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

38 Grazie per la vostra attenzione Grazie per la vostra attenzione

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