«Focus on: La Sincope»(in attesa delle linee guida ESC 2018)

Syncope Unit. Geriatria e Terapia Intensiva Geriatrica

Università degli Studi di Firenze e Azienda Ospedaliero Universitaria Careggi - Firenze

Andrea Ungar, MD, PhD, FESC

«La Sincope»

Definizione e fisiopatologia

Definizione

La sincope è una perdita di coscienza transitoria dovuta ad ipoperfusione cerebrale globale, caratterizzata da

rapida insorgenza, breve durata,

recupero completo e spontaneo

2009 ESC guidelines

Perdita di coscienza?

NO

Cadute

Modalità di presentazione della Perdita di Coscienza Transitoria

Coscienza Alterata Altro

SI

Transitoria?Rapido esordio?

Breve durata?Recupero

spontaneo?

Coma Altro

NO

PdCT

SI

Sincope Epilessia Funzionale Forme rare

Non traumatiche Traumatiche

2009 ESC guidelines

Il meccanismo fisiopatologico

sottostante la sincope è una ipoperfusione cerebrale globale

transitoria

Poligono del Willis

In condizioni di normale

funzionamento del poligono

del Willis, la causa della

sincope è per definizione

“extracranica”

«La Sincope»

Inquadramento, stratificazione e gestione

ESC Guidelines 2009

History, physical examination,

orthostatic BP measurements,

ECG

And

Carotid sinus masage (CSM)

in patients > 40 years

ESC Guidelines 2009

Eur Heart J 2010

Ungar A et al, Eur Heart J 2010, in press

Ungar A et al, Eur Heart J 2010, in press

Long term mortality

Syncope in those with structural heart disease

triples probability of death [OR 3.0 (95% CI 1–10)].

The outcome of arrhythmic syncope, instead, is

more favourable and not different from the

syncope forms usually considered as benign such

as neurally mediated and orthostatic hypotension

EGSYS score < 3: cardiac syncope is unlikely

EGSYS score > 3: cardiac syncope is probable

Specificity 69%

Sensitivity 95%

SINCOPE2 0 1 7

www.gimsi.it

Casagranda I. et al 2016

Casagranda I et al 2016

SINCOPE2 0 1 7

www.gimsi.it

«What to do» in admitted patients in Observation unit

for unexplained syncope (24-48 hours)

24-48 hours ECG Monitoring :monitor, telemetry

Blood chemistry:second troponin evaluation, anemia, electrolyte disturbances

Cardiac evaluation:echocardiogram, stress test, TC-scan for Pulmonary embolism or coronary evaluation if appropriate

History revaluation:particularly if witness are necessary and not present in ED

First line short treatmentelectrolyte disturbances correction, red blood cells transfusion

……………………………………

Assessment of a novel management

pathway for patients referred to the

Emergency Department for syncope: results

in a Tertiary Hospital

(Careggi Hospital - Florence, Italy)

Ungar a et al, Europace 2015

SINCOPE2 0 1 7

www.gimsi.it

Consecutive patients referred to the EDof Careggi Hospital for T-LOC in whichsyncope was suspected as the maindiagnosis, from 1 January to 30 June2010

SINCOPE2 0 1 7

www.gimsi.it

Consecutive patients referred to the EDof Careggi Hospital for T-LOC in whichsyncope was suspected as the maindiagnosis, from 1 January to 30 June2010

SINCOPE2 0 1 7

www.gimsi.it

ED

295 patients

Admitted

85 pz

(29%)

Short stay

60 pt

(20%)

Syncope Unit

Fast Track

58 pt

(21%)

Discharded

92 pt

(31%)

29% vs 39% EGSYS 2

SINCOPE2 0 1 7

www.gimsi.it

0.1

.2.3

.4.5

0 5 10 15Months of follow-up

Ricovero OBI

Fast Track Niente

Rifiuta

Estimated hospital re-admission according to multivariable Cox model-destino

New admissions related to ED destination

1 month 12 months

Follow-up

Admission Short stay observation Syncope Unit DimissionRefusal

No patients sent to Syncope Unit

was dead within one year

Our outcomes prove the safety of the model

recommended by 2009 ESC guidelines

Ungar a et al, Europace 2015

SINCOPE2 0 1 7

www.gimsi.it

1-month-mortality rate was 0.03% (1/295)12-months-mortality rate was 5.4% (16/295)No events between ED and SU evaluation

SINCOPE2 0 1 7

www.gimsi.it

SINCOPE2 0 1 7

www.gimsi.it

Kenny R.A. et al. 2015

Causes of Syncope in general population (EGSYS 2) and in geriatric departments (GIS)

Cardiac

Neuromediated

Orthostatic

Cerebrovascular

Drug Induced

Unexplained

n (%)

8 (11.3)

44 (62)

3 (4.2)

0

3 (4.2)

10 (14.1)

n (%)

26 (16.3)

58 (36.3)

49 (30.5)

0

8 (5)

14 (8.8)

ns

0,001

0,001

/

ns

ns

65-75 years(n=71)

> 75 years(n=160)

p*

n (%)

74 (16)

309 (66)

46 (10)

0 (0)

2 (0)

11 (2)

All(n=465)

GIS**

* <75 years vs >75 years GIS

* Brignole M et al, Eur Heart J. 2006; 27:76-82 ** Ungar A et al, JAGS 2006; 54: 1531-1536

EGSYS 2*

In Older patients Orthostatic

Hypotension must be

evaluated in all patients

Gruppo Italiano Sincope (GIS) - SIGG

Syncope and Dementia, a GIS Registry

SYD Registry

We enrolled patients with Syncope and Unexplained falls

Aging clin exp res, 2015

SYD

registry

Aging clin exp res, 2015

SYD

registry

Ungar a. et al, JAGS 2016

SYD

registry

Ungar a. et al, JAGS 2016

SYD

registry

Ungar a. et al, JAGS 2016

SYD

registry

www.gimsi.it

STOP-VDStop vasodepressor drugs in reflex syncope

A randomized controlled trial

Bolzano, 20 febbraio 2016

Diana SolariFrancesca TesiMatthias UnterhuberGermano GaggioliAndrea UngarMarco TomainoMichele Brignole

From the Syncope Units of:

Ospedali del Tigullio, Lavagna

University of Firenze

Ospedale Generale, Bolzano

Ospedale Villa Scassi, Genova

A trial sponsored by GIMSI

AIM OF THE STUDY

to investigate the clinical effects of discontinuation of vasoactive drugs in patients affected by vasodepressor reflex syncope

Randomized, parallel, prospective, safety/efficacy study conducted from January 2014 to December 2015 in 4 general hospitals (Lavagna, Genova, Firenze, Bolzano)

END-POINT: recurrence of

- syncope - pre-syncope

- adverse events: stroke, TIA, worsening HF, AMI

PATIENTS AND METHODS

INCLUSION CRITERIA:

• ≥2 episodes of reflex syncope during the previous year

• 1 or more vasoactive drugs (antihypertensive agents,

nitrates, diuretics, neuroleptic antidepressants or L-dopa antagonists)

positivity of TILT TABLE TEST and/or CSM for a VD FORM

EXCLUSION CRITERIA:

• orthostatic hypotension• severe hypertension (office BP >150/95) poorly controlled with

ongoing therapies• severe structural heart disease

• previous transient cerebral ischemic attack or stroke.

Clinical Characteristics

Results

Characteristics Stop/reduce

therapy

(n=30)

Continue

therapy

(n=24)

P

value

Mean age, years 75 + 12 73 + 11 0.54

Male sex 18 (58%) 10 (42%) 0.28

History of arterial hypertension 29 (94%) 23 (96%) 1.00

Structural heart disease 9 (29%) 5 (21%) 0.55

Depressive disorders 3 (10%) 3 (12%) 1.00

Median number of syncopes in

the last yeas

2.0 (1.3-3.0) 2.0 (1.8-3.0) 0.99

Mean number of vasoactive drugs

per patient

2.4 + 1.1 2.5 + 0.9 0.77

MAIN RESULTS: SYNCOPE, PRE-SYNCOPE AND ADVERSE EVENTS

Outcome Stop/reduce therapy

(n=31)

Continue therapy

(n=24)

Hazard ratio

(95% CI)

p value

Primary combined end-point (syncope and/or pre-syncope and/or adverse event)

6 (19%) 12 (50%) 0.37

(0.14-0.95)

0.03

Recurrence of syncope and/or pre-syncope 6 (19%)*

11 (46%) 0.41

(0.15-1.05)

0.05

Recurrence of syncope 2 (6%) 9 (37%) 0.17

(0.05-0.55)

0.007

Assessment at 1 month:

- Office supine SBP, mmHg 141±13 128±14 0.001

- Office standing SBP, mmHg 133±13 122±15 0.006

- Home daily SBP (average of 30-day measurements)

141±15 133±16 0.06

- SSS-OI Questionnaire: total score (score 0-70) 7.2±8.8 13.1±10.6 0,04

Mean follow-up: 9±7 months

p = 0.03

Stop/reduce

Continue

SYNCOPE, PRE-SYNCOPE AND ADVERSE EVENTS

Mean follow-up: 9±7 months

p = 0.007

Stop/reduce

Continue

SYNCOPE

Mean follow-up: 9±7 months

«La Sincope»

Il monitoraggio

Recommendations: Electrocardiograhic monitoring

I B• Immediate in-hospital monitoring (in bed

or telemetric) is indicated in high risk

patients

• Holter monitoring is indicated in patients

who have very frequent syncope or pre-

syncope (≥1 per week)

I C

Recommendations: Electrocardiograhic monitoring

• Il monitoraggio è diagnostico se vi è una correlazione

tra sintomo e aritmia

• In assenza di correlazione sono diagnostici un blocco

atrioventricolare avanzato, una pausa ventricolare > 3

secondi, o una tachicardia atriale ad elevata frequenza

• Le altre aritmie asintomatiche non hanno rilievo

diagnostico

• La bradicardia sinusale in assenza di sintomi non è

indicativa della causa di sincope

• La presincope non è diagnostica

NMS at initial evaluationILR implantation

504

Diagnosis after ECG documentation

Follow-up: 15±11 months

187 (37%)

Hypotensive NMS

63 (34%)

Asystolic NMS

99 (53%)

Intrinsic cardiac

arrhythmias21 (11%)

Non-arrhythmic

T-LOC4 (2%)

NMS likely 162 (87%)

NMS excluded25 (13%)

ISSUE 3

SYNCOPE

Diagnosis

Ungar A. et al, heart 2013

ISSUE 3

SYNCOPE

Diagnosis

Intrinsic cardiac arrhythmias

21 (11%)

Non-arrhythmic T-LOC4 (2%)

NMS excluded25 (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

«La Sincope»

Due peculiarità:1. Le cadute non spiegate

Le cadute

Definizioni di caduta:

Caduta accidentale:caduta spiegata da circostanze accidentali certe

Caduta da causa “medica”:cadute con nesso casuale diretto con causa medica

specifica (ad es. ipoglicemia, iatrogene, attacco ischemico

transitorio, drop-attack, infarto miocardio acuto, aritmie,

ipotensione ortostatica etc.)

Caduta associata a demenza:caduta in pazienti con diagnosi pregressa di demenza

moderata-severa (MMSE <18/30)

Caduta “non spiegata”:caduta non accidentale e non legata a cause

mediche o iatrogene (patologia acuta o iatrogena)

Unexplained fall in older patients, UFO, submitted

Unexplained falls are frequent in patients with fall-related injury

admitted to orthopaedic wards: the UFO study (Unexplained Falls

in Older patients).

All

(n=246)

65-79 years

(n=79)

≥ 80 years

(n=167)

p

Remember the event 78.9 92.2 72.3 0.002

Witness presence 39.4 45.3 36.6 ns

Syncope 8.1 7.4 8.3 ns

Fractures 92.6 90.0 93.9 ns

Prodroms 17.9 17.7 18.0 ns

Unexplained fall in older patients, UFO, Mussi c. et al 2013

Unexplained falls are frequent in patients with fall-related injury

admitted to orthopaedic wards: the UFO study (Unexplained Falls

in Older patients).

All

(n=246)

65-79 years

(n=79)

≥ 80 years

(n=167)

p

Accidental (%) 99 (40.2) 38 (48.1) 61 (36.5) 0.02

Medical (%) 25 (10.2) 7 (8.9) 18 (10.8) n.s.

Dementia-related (%) 31 (12.6) 5 (6.3) 26 (15.6) 0.02

Unexplained (%) 91 (37.0) 29 (36.7) 62 (37.1) n.s.

Unexplained fall in older patients, UFO, Mussi c. et al 2013

Amnesia for Loss of Consciousness

in Carotid Sinus Syndrome

Implications for presentation with falls

Parry SW et al. JACC 2005; 45: 1840

Falls

(n=34)

Syncope

(n=34)

Am

nesia

(%

)

95%

27%

0

20

40

60

80

100

Caduta accidentale …….

… o caduta non spiegata???

Sincope, Demenza, “Dizziness”,

Ipotensione ortostatica, Aritmie …

Unexplained

Falls

Unexplained

Syncope

Older patients

Syncope

diagnostic

protocol ?ESC guidelines 2009

Syncope Unit – Geriatric Cardiology

University of Florence, Italy

Patients referred for neuroautonomic evaluation from

July 2002 to June 2011

989 patients

with unexplained syncope

298 patients

with unexplained fall

Diagnosis was obtained at the and of clinical and

neuroautonomic evalutation (OH, TT, CSM) in 64% of

patients with syncope and in 61% of patients with fall (p=ns)

0

4000

8000

12000

Pati

en

ts (

n)

Causes of falls in 24,251 patients >50-year old

admitted to an emergency department

Kenny RA et al. JACC 2001; 38: 1491

Accidental

41%

Medical disease

27%

Dementia

17%

Unexplained

15%

3637 patients

Attività del DEA se decidiamo di studiare le cadute non

spiegate come fossero dei possibili episodi sincopali

71.299 pazienti che afferiscono al DEA con età > 50anni

2.139 (3.0%) pazienti con sincope

23.112 (32.4%) pazienti con caduta

Insieme sono il 35.4% di tutti gli accessi

Patienti con sincope non spiegata : 30% (n=642)

Patienti con caduta non spiegata: 15% (n=3384)

4026 patienti (5.64% di tutti gli accessi in DEA)

dovrebbero essere valutati come pazienti con

transitoria perdita di coscienza di origine non spiegata

Mod da: Kenny RA. 2001 (SAFE PACE); Kenny RA. 2002

Attività del DEA se decidiamo di studiare le cadute non

spiegate come fossero dei possibili episodi sincopali

Abbiamo bisogno di

Syncope and Falls Unit

per valutare questi

pazienti

«La Sincope»

Due peculiarità:2. La sincope adenosino-

mediata

«La Sincope»

Grazie per la vostra attenzione