Quando è

realmente utile

la chiusura

percutanea

dell’auricola

sinistra?

Gennaro Santoro , Firenze

Fondazione CNR-Regione Toascana G.Monasterio

per la Ricerca Medica e la Sanità Pubbica

santorogenn@gmail.com

DISCLOSURE INFORMATION

negli ultimi due anni non ho avuto rapporti di finanziamento con soggetti portatori di interessi commerciali in campo sanitario

NESSUN CONFLITTO DI INTERESSE

Gennaro Santoro

Firenze

santorogenn@gmail.com

Profilassi dello stroke cardioembolico in

FA

Le opzioni terapeutiche

Terapia farmacologica

Terapia meccanica percutanea

Terapia meccanica chirurgica

(non valvolare)

ACC/AHA 2014: CHA2DS2-VASc ≥ 2

ECS 2012: CHA2DS2-VASc ≥ 1*

CCS 2012: CHADS2 ≥ 1

* Eccetto donne con lone FA

JACC 2014. CJC 2012;28:125-136. EHJ 2012;33:2719-2747

Rischio di sanguinamento

HAS-BLED ≥ 3 NOAC/Warfarin

TAO a lungo termine

Sanguinamenti

Compliance

Efficacia TAO efficace se TTR > 70%

Prevalence of irreversible contraindication* to OAC in

general AF population depending on age and gender

* SPAF III study: Major bleeding previous 6 months, frequent falls, inability to comply to treatment,

excessive alcohol consumption, (uncontrolled hypertension, daily use of NSAIDs)

34%

7%

35%

14%

0%

10%

20%

30%

40%

Women Men

> 75 years

65-75 years

Sudlow M et al. The Lancet 1998

55.5

% 2012 2010 2012 2007 2008

71.6 64.2

46.3 46 42.7

38

Prevalenza della TAO in Registri Italiani Contemporanei

CARD

CARD

Totale

MED MMG Post

dimissione Database

HSD

PREFER in AF 3

(N=1888)

ATA AF 9

FA non valvolare

(N=7148)

ISAF 12

(N=6036)

ARNO 14

(N=2605)

OSMED 15

FA ad alto rischio

di ictus

(N=9204)

20

40

60

80

Di Pasquale G et al. G Ital Cardiol 2014

Age-related trends in AF

Age, years

69-79 80-89 >89

100

80

60

40

20

0

Unmet need

Wolf PA, Arch Intern Med 1987; 147:1561-4

White RH, Am J Med 1999; 106:165-71

Profilassi dello stroke cardioembolico in

FA

Le opzioni terapeutiche

Terapia farmacologica

Terapia meccanica percutanea

Terapia meccanica chirurgica

(non valvolare)

PERCHÉ CHIUDERE L’AURICOLA SINISTRA?

Ra

zio

na

le p

er l’o

cc

lus

ion

e

dell’a

uric

ola

sin

istra

Ann Thorac Surg 1996; 61: 755-759

90% of clots form in the LAA

COME CHIUDERE L’AURICOLA SINISTRA?

Le modalità di chiusura

dell’auricola sinistra

• Atritech-4° generation device

• AGA -ACP device

• Occlutech

• Coherex

• Custom Medical Devices (Sideris Patch)

• Gore

• ………

Approccio endocardico

Approccio epicardico

• AtriCure

• Epitek

• Medtronic

• SentreHeart

Monitoraggio della Procedura

Posizione del device

Concovità lieve del disco

Spazio fra disco e lobo

Lieve tenting posteriore del lobo

Assenza di flusso in auuricola sinistra

RISULTATI CLINICI DELLA CHIUSURA PERCUTANEA

Studi osservazionali

PROTECT AF Clinical Trial Design

Prospective, randomized study of WATCHMAN LAA Device vs. Long-term Warfarin Therapy

2:1 allocation ratio device to control Non-inferiority comparison 800 Patients enrolled from Feb 2005 to Jun 2008-707

randomized 59 Enrolling Centers (U.S. & Europe) Follow-up Requirements

TEE follow-up at 45 days, 6 months and 1 year Clinical follow-up biannually up to 5 years Regular INR monitoring while taking warfarin

Enrollment continues in Continued Access Registry

Primary Efficacy Endpoint All stroke: ischemic or hemorrhagic

• deficit with symptoms persisting more than 24 hours or • symptoms less than 24 hours confirmed by CT or MRI

Cardiovascular and unexplained death: includes sudden death, MI, CVA, cardiac arrhythmia and heart failure

Systemic embolization

Primary Safety Endpoint Device embolization requiring retrieval Pericardial effusion requiring intervention Cranial bleeds and gastrointestinal bleeds Any bleed that requires ≥ 2uPRBC

NB: Primary effectiveness endpoint contains safety events

PROTECT AF Trial Endpoints

Lancet 2009

0,7

0,8

0,9

1,0

0 365 730 1095

Intent-to-Treat: Hemorrhagic Stroke

ITT cohort: Superiority criteria met

Eve

nt-

fre

e p

rob

abili

ty

Days 244 147 53 12

463 275 95 23

WATCHMAN

Control

3000838-103

900 patient-year analysis

Events Total Rate Events Total Rate RR Non- Superiority Cohort (no.) pt-yr (95% CI) (no.) pt-yr (95% CI) (95% CI) inferiority

600 1 416.7 0.2 4 224.7 1.8 0.13 0.998 0.986 pt-yr (0.0, 0.9) (0.5, 3.9) (0.00, 0.80)

900 1 593.6 0.2 6 319.4 1.9 0.09 >0.999 0.998 pt-yr (0.0, 0.6) (0.7, 3.7) (0.00, 0.45)

Device Control Posterior probabilities

Randomization allocation (2 device:1 control)

12,3%

Pericardial effusion requiring drainage 4,8%

- reduction 50% > 3 cases- none disabiling

Periprocedure ischemic stroke 1,1%

- air or thromboemboli

Device removal

-embolization or sepsis n=4

Thrombus on device in 3,7%

-clopidogrel x 6 months

Learning curve effect substantial

PROTECT AF Procedural Complications

Reddy et al Circulation 2011

PROTECT AF & CAP Registry: Safety events

PROTECT-AF follow up

PROTECT AF: efficacia al follow-up

WATCHMAN – PREVAIL

Primary Efficacy Endpoint All stroke: ischemic or hemorrhagic

deficit with symptoms persisting more than 24 hours or symptoms less than 24 hours confirmed by CT or MRI

Cardiovascular and unexplained death: includes sudden death, MI, CVA, cardiac arrhythmia and heart failure

Systemic embolization

Late ischemic Efficacy Endpoint Ischemic stroke or SE excluding the first 7 days after randomization

Early safety primary endpoint All cause of death Ischemic stroke SE Device/procedure related events

between randomization and within 7 days of the procedure

3 CO-PRIMARY ENDPOINTS

PRIMO END POINT PRIMARY EFFICACY END-POINT

Statistical noninferiority was not

achieved

SECONDO END POINT LATE ISCHEMIC EFFICACY END-POINT

Statistical noninferiority was achieved

INCLUSION CRITERIA

• Age > 18 years,

• Nonvalvular AF (paroxysmal,

persistent, or permanent)

• CHADS2 score ≥ 1

• Contraindication for even short-

term oral anticoagulation

therapy, and eligibility for 6

months of treatment with a

thienopyridine antiplatelet agent

(clopidogrel or ticlopidine) and

lifelong aspirin.

EXCLUSION CRITERIA

• Left ventricular ejection fraction < 30%

• Intracardiac thrombus/dense

spontaneous contrast by

transesophageal echocardiography

• A patent forman ovale with atrial septal

aneurysm

• Complex atheroma with mobile plaque

in the ascending aorta/aortic arch,

significant mitral stenosis, or an existing

pericardial effusion > 3 mm

OAC CONTRAINDICATION

1) hemorrhagic/bleeding tendencies defined

as active peptic ulcer disease or history of

overt bleeding of the gastrointestinal,

genitourinary, or respiratory tract; central

nervous system hemorrhage, cerebral

aneurysms, dissection of the aorta,

pericarditis/pericardial effusions or bacterial

endocarditis;

2) blood dyscrasias;

3) unsupervised patients with senility and/or

high fall risk

4) other documented reason (including

hypersensitivity to warfarin).

ASAP – risultati

ACP

Risultati con ACP

• Successo procedurale: 97,6%

• Stroke periprocedurale: 0,38%

• Embolizzazione del device: 0,67%

• Versamento pericardico (trattato): 1,25%

• Complicanze periprocedurali: 2,8%

• Stroke al follow-up: 0,62%

Meier B et al, Europace 2014

EuroIntervention 2014, in press

Results

Stroke rate reduction

8,6%

1,5%

0%

5%

10%

Expected stroke rate based on CHADS

Observed stroke rate in the study (median=3)

Bleeding rate reduction

5,4%

3,5%

0%

3%

6%

Expected bleeding risk based on HAS-BLED

Observed major bleeding rate in the study (median=3)

p < 0,01

- 82%

- 35%

INDICAZIONI ALLA CHIUSURA PERCUTANEA

Indicazioni proposte alla chiusura percutanea dell’auricola sinistra

Documento di posizione sui requisiti di processo diagnostico ed interventistico riferiti al trattamento

della chiusura dell’auricola sinistra in pazienti affetti da fibrillazione atriale non valvolare

Società Italiana di Cardiologia Invasiva GISE.

In pazienti con alto rischio di tromboembolismo (CHA2DS2VaSc >=2)

Controindicazione all’anticoagulazione o alto rischio emorragico (HAS-BLED >=3)

Pazienti anziani con FA e DES

Recidiva di stroke in corso di TAO ben condotta

Indicazioni

• NICE 2010 –

• ESC 2012 –

• GISE/AIAC 2014 –

• FDA – Watchman

• EHRA/EAPCI 2014

Contraindication to OAC

Increased bleeding risk

As alternative to oral

anticoagulation

Cardiochirurgia

• NICE 2010 – Cardiac surgery on-site

• EHRA/EAPCI 2014 – Cardiac surgery center at 60 min (operating

room)

• GISE/AIAC 2014 – Cardiac surgery on-site

Thank you for your

attention!

Clinical

Cardiologist Neurologist

Cardiac

Surgeon

Electrophysiologist

Echo

Team Interventional

Cardiologist