Fibrilatia atriala

Adriana Gurghean
Sibiu, august 2014

Date epidemiologice

1,5-2% populatia generala

5-15% la varstnici
1/20 AVC acute
riscul de aparitie a FiA > 40 ani = 25%
mai frecventa la barbati
risc de AVC de 5x mai mare; frecvent fatal
risc de IC de 3x mai mare !!!

Screening FiA
EMBRACE

pac

& CRYSTAL-AF - > 1000

pac cu AVC criptogenetic monitorizati

prelungit: 1luna / monitor implantabil
au evidentiat episoade de FiA de 5x
mai frecvente fata de martor

NEJM, june 2014

Riscul de evenimente
cardiovasculare

Deces cardiovascular dublu

Insuficienta cardiaca 30-40% si invers
CM tahiaritmica
AVC acelasi risc pentru toate formele de FiA
Spitalizari frecvente 1/3 spitalizarile pentru
TR
Disfunctie VS asimptomatica
Toleranta redusa la effort
Scaderea calitatii vietii

Asocieri frecvente cu FiA

Varsta
Insuficienta cardiaca
Valvulopatii degenerative
Cardiomiopatii
Boli congenitale DSA 10-15%
Ischemia miocardica 20% FiA
Distiroidii
Obezitate 25% din FiA
Diabet 20% din FiA
BPOC 10-15% din FiA
Sleep-apnoea
BCR 10-15% din Fia

Mecanismele de aparitie a FiA

anomalii structurale V si A

disociatie intre fb mm
si conducere electrica
circuite mici de reintrare
initiere
perpetuare
stabilitate

Mecanismele electrofiziologice
si predispozitia genetica

Focare anormale

mec celulare: automatism / reintrare

v pulm (FiA parox) / dispersate (FiA persist)

Unde multiple

conducere continua, haotica, independenta

Predispozitia genetica

- sdr QT lung / scurt; preexcitatie V

- CMH
- mutatii gene: ANP, hipofct can Na, Hfct can K

Consecintele fiziopatologice
ale FiA

EF: PRE : primele zile

down-reglarea curenti Ca tip L
up-reglarea curenti rectificatori de K

Mecanic: contractilitate ineficienta: zile

down-reglarea curentilor de Ca
scaderea eliberarii Ca din depozite
modificarea prop energetice miofibrilare

Principalele consecinte clinice

Alterarea hemodinamicii
pierderea contractiei atriale
frecventa V crescuta, neregulata
scaderea fluxului miocardic
cardiomiopatia A si V

Accidentele tromboembolice
anomalii ale fluxului: staza AS si US
anomalii ale componentelor sg: activare
plachetara, hemostaza, inflamatie, factori
de

Clasificarea FiA

1. Primul episod de FiA indiferent de durata /

severitatea simptomelor

2. FiA paroxistica max 48 h

3. FiA persistenta - > 7 zile / necesita cardioversie

4. FiA persistenta lunga - > 1 an

5. FiA permanenta acceptata de pacient/dr **

FiA asimptomatica oricare din cele 5 forme/dg

ocazional sau printr-o complicatie

Evolutia naturala a
FiA

AF = atrial fibrillation

Tipuri de FiA

Lone AF fara o boala cardiaca

structurala

FiA non-valvulara
absenta SMi, proteze valvulare, plastie
VMi

FiA secundara
ex. infectii acute

Evaluarea clinica
Evaluarea

simptomelor (scorul EHRA)

Estimarea

riscului de AVC

Dg

conditiilor predispozante pt FiA

Evaluarea

complicatiilor

Evaluarea clinica initiala

Momentul instalarii FiA tip FiA
Semne de IC acuta
control urgent AV
cardioversie
eco fct VS, PsVD, valve
AIT / AVC CT +/- revascularizare
Evaluare risc AVC: ACO
Evaluarea cauzelor
eco cord
fctie tiroida
HLG, creat, glicemie
teste stress pt ischemie
coronarografie (persist disf)

Tratamentul FiA

Ameliorarea simptomelor
controlul ritmului
controlul frecventei

Prevenirea complicatiilor
tratamentul antitrombotic

Tratamentul conditiilor
asociate

Urgenta !!! SEE sincron

Controlul ritmului in FiA

Cardioversia

farmacologica sau electrica

a FiA persistente sau supresia
episoadelor recurente de FiA paroxistica

!!!

Mentinerea indicatiei de
anticoagulare chiar daca optam pentru
controlul ritmului
Pacientii cu FiA paroxistica = acelasi risc de
AVC si embolic ca si cei cu FiA persistenta !

Conversia electrica a FiA

SEE sincron 200-360 J

Sedare / midazolam
In urgenta : simpt severe /
degradare hemodinamica / WPW
Electiva : stabili
ACO 3 sapt ant
FiA< 48 h - control TEE si
conversie
+/- pretratament AA

DC cardioversion for
AF

Class of recommendation. bLevel of evidence.

AF = atrial fibrillation; DCC = direct current cardioversion.
a

Drugs and doses for

pharmacological
conversion of (recent-onset) AF

ACS = acute coronary syndrome; AF = atrial fibrillation; DCC = direct current cardioversion; i.v. = intravenous;
N/A = not applicable; NYHA, New York Heart Association; p.o. = per os; QRS = QRS duration; QT = QT interval;
T-U = abnormal repolarization (T-U) waves.

Cardioversia farmacologica
Vernakalant
FiA < 7 zile / < 3 zile
postinterv cardiace
Actiune: atrial
Prelungeste PRA si
scade conducerea A
Instalare efect: rapida
T1/2 = 3-5 ore

Vernakalant - studii
Superior Amiodarona
Eficient la:
HTA
Ischemie
postoperator
+/-: IC
Ineficient in: FiA > 7
zile/ FlA tipic

Vernakalant reactii adverse si

contraindicatii

Reactii adverse

Hipotensiune arteriala 5-7% (16% in IC)

Bradicardie 0,5%
TR-V in IC 7,3% TVNS
Alungirea QT si QRS

Contraindicatii

TAs < 100 mmHg

SCA < 30 zile
IC NYHA III-IV
SAO severa
QT > 440msec
FE < 35 %

Terapia antiaritmica orala

I:

preventia FiA recurenta

(persistenta / paroxistica)

!!Eficienta

crescute

Controlul

vs reactii adverse si Mo

simptomelor persistente
date de recurenta FiA

Antiaritmicele orale pe ce durata

?
Flec-SL

(Flecainide Short Long)

635 pts, (B 64%, 64 ani, HFPEF, 6 luni)

3 brate: fara AA; short (4sapt); long
Short: protectie 80% long la 6 l
Amiodarona

Long (t1/2 lung)

Short (episodic) daca: r adv sint mici sau
recurentele sint rare
Dronedarona

Dronedarona in mentinerea RS
Structura
Blocant

asemanatoare A

multiplu:

canale Na si K
antiadrenergic
prop asemanatoare Ca blocantelor
Eficienta:

superior placebo/ inferior A

Dronedarona - studii

Dronedarona I si CI
I:

FiA paroxistica / persistenta post conv.

IC NYHA I II cu FE pastrata
CI:

FiA permanenta (PALLAS)

IC NYHA III-IV (ANDROMEDA)
Instabilitate hemodinamica
Disfunctie sistolica VS

Choice of an antiarrhythmic
drug
for AF control

Class of recommendation. bLevel of evidence.

AF = atrial fibrillation; AV = atrioventricular; LoE = level of evidence; NYHA = New York Heart Association.
a

Concluzii terapia AA orala pt

controlul ritmului

Recurenta FiA la pacientii cu

AAD

77% - RFCA vs 19% - 52% AAD !

Yun-Yu Chen, BS.

2013

Limite / complicatii ale ablatiei

Limite ale eficacitatii

FiA persistenta lunga (>1 an)

AS dilatat (>55 mm)
Age > 70 years
Patologie structurala cardiaca
Recurente mai frecvente pe termen lung

Complicatii
-

TC, pericardita, fistula A-E, stenoza VP

Vasculare periferice
Infarct cerebral silentios (MRI) 4-35%

39

Ablatia in FiA cu IC

Eficienta neclara in IC cu
disfunctie VS
Amiodarona e I indicatie
I: simptome legate de FiA
sub amiodarona
ACO = obligatorie
Rata mentinerii RS e mica
Riscurile procedurale mult
mai mari
Ameliorarea functiei VS ?

Ablatia pe cateter vs ablatia

chirurgicala
Studiul

FAST

A chirurgicala eficienta > in controlul

ritm
A chirurgicala - complicatii >
Dificultati tehnice

Ablatia chirurgicala

maze procedure

Succes 75-95% la 15
ani

Complic si Mo crescute

FiA + BMi

Evaluarea preablatie

Holter ECG

Eco cord: afectare structurala

MRI, CT: fibroza A

TEE: excludere tromb AS, US

ACO preablatie

Controlul Frecventei
in
Fibrilatia Atriala

Efectele functionale ale FiA

Pierderea

pompei atriale

In caz de HVS reducerea volumului bataie

cu peste 25 %
Scurtarea

diastolei umplere deficitara

Tahicardia de efort simptome de efort
Miocardiopatia tahicardica

Insuficienta cardiaca

Cind trebuie redusa

frecventa ?
Terapia
Pina

initiala

la deciderea conversiei

Prevenirea

frecventei inalte in FA
paroxistica si persistenta recurenta

FA

cronica

Cum alegem intre controlul frecventei si controlul ritmului in FiA persi

Quality of
life
Morbidity
Mortality

Controlul ritmului vs controlul

frecventei

Impactul FiA cronice asupra evolutiei

Probabilitatea de mentinere a RS

Severitatea simptomatologiei legate

de FiA

Factori ce pot influenta mentinerea RS

Factori ce influenteaza negativ

mentinerea RS
Istoric

indelungat de FiA

Virsta
Boala

cardiovasculara severa
coexistenta
Comorbiditati
AS dilatat

Cine ar beneficia cel mai mult de

controlul frecventei ?

Controlul frecventei pe termen

lung

Controlul frecventei pe termen

lung

Care este frecventa

optima ?
AFFIRM (60-80bpm
rep; 90-115bpm effort
moderat)

<110bpm, rep

Controlul nefarmacologic al
frecventei
Ablatia

nodului AV

paliativa, ireversibila
esecul terapiei farmacologice
Modificarea

NAV radiofrecventa

mai putin eficienta

Implantare

DDD, CRT)

PM fctie de tipul FiA (VVI,

Tratamentul antitrombotic
in FiA

Factorii de risc tromboembolic in

FiA

Antecedente de accidente TE
Varsta
Diabet zaharat
HTA
Boli structurale cardiace
Disfunctia sistolica VS moderat-severa (TTE)
Tromb prezent in AS (TEE)
Placi complexe Ao (TEE)
Contrast spontan, viteze mici US (TEE)

Riscul tromboembolic in FiA

(scor CHADS2)
2 = istoric AVC / AIT
1=

varsta > 75 ani

HTA
IC
DZ

Scor 0 = risc mic

Scor 1-2 = risc moderat
Scor > 2 = risc crescut
>2 = ACO cronic

Limitele scorului CHADS2

Categoriile de risc mai degraba artificiale

Beneficii ACO vs aspirina si la cei cu risc

moderat

Nu include multi alti FR-TE

Majoritatea schemelor de risc cu VPP mica

pt AVC

Scorul CHA2DS2 - VASc

Aprecierea riscului hemoragic

HEMORR2 HAGES
Hepatic or renal disease, Ethanol abuse, Malignancy, Older
(>75), reduced platelet count/function, Rebleeding risk,
Hypertension, Anemia, Genetic factors, Excessive fall risk,
Stroke

HAS-BLED
Hypertension, Abnormal liver/renal function, Stroke,
Bleeding history, Labile INR, Elderly, Drugs/alcohol

ATRIA
AnTicoagulation and Risk factors In Atrial
fibrillation

Terapia antitrombotica in FiA

Aspirina
Clopidogrel
Antivitamina

Antitromboticele

noi

Aspirina in FiA
Metaanaliza

8 studii (4876 pts)

reducerea RA cu 0,8%/an prev I

reducerea RA cu 2,5%/an prev II
Se
FiA

prefera dozele mici (<100mg)

izolata beneficiu mic / risc

hemoragic mare (1,6% vs 0,4% placebo)

Aspirina + Clopidogrel in FiA

ACTIVE-W: CLO+ASA vs WAR

WAR superioara (reducere RR AVC isch cu 40%)
WAR acelasi risc hemoragic

ACTIVE-A: CLO+ASA vs ASA

CLO+ASA superior / risc hemoragic mare
Concluzii: CLO+ASA doar daca ACO e CI

Antivitamine K in FiA
Reducerea

RR AVC ischemic cu 67%

INR terapeutic
Rezultate

similare pentru preventia I si II

Reducere

Mo generala cu 26%

Indicatie:

orice FiA + cel putin 1 FR AVC

Current Trial-Associated Outcomes With Warfarin in

Prevention of Stroke in Patients With Nonvalvular Atrial
FibrillationA Meta-analysis

S. Agarwal et al, Arch.

Intern. Med, 2012

Recomandarile pentru
profilaxie

Anticoagularea
pericardioversie

Anticoagularea
pericardioversie

Anticoagularea, FiA si AVC

acut

Anticoagularea, FiA si interventiile

chirurgicale

Anticoagularea, FiA si
stenturile

Anticoagularea periablatie
Previne

TES indiferent de FR
Nu se intrerupe/se scade daca e
nevoie
E recomandata postablatie pe
termen lung la scor > 2.
ACO noi nu exista experienta

Anticoagulantele noi

Inhibitori directi ai trombinei dabigatran

(RE-LY)

Inhibitori directi ai factorului Xa rivaroxaban

(ROCKET-AF) / apixaban (ARISTOTLE)

Dabigatran versus Warfarin in Patients with

Atrial Fibrillation (RE-LY)

In a large, randomized trial, two doses of the

direct thrombin inhibitor dabigatran were
compared with warfarin in patients who had
atrial fibrillation and were at risk for stroke

Efficacy Outcomes, According to Treatment Group

Connolly SJ et al. N Engl J Med 2009;361:1139-1151

Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism,
According to Treatment Group

Connolly SJ et al. N Engl J Med 2009;361:1139-1151

Rata accidentelor hemoragice

Conclusion
In patients with atrial fibrillation, dabigatran

given at a dose of 110 mg was associated

with rates of stroke and systemic embolism
that were similar to those associated with
warfarin, as well as lower rates of major
hemorrhage
Dabigatran administered at a dose of 150
mg, as compared with warfarin, was
associated with lower rates of stroke and
systemic embolism but similar rates of
major hemorrhage

Rivaroxaban versus Warfarin in Nonvalvular

Atrial Fibrillation (ROCKET-AF)

In this trial, 14,264 patients with atrial

fibrillation were randomly assigned to receive
either rivaroxaban or warfarin.

Primary End Point of Stroke or Systemic Embolism.

Patel MR et al. N Engl J Med 2011;365:883-891

Cumulative Rates of the Primary End Point (Stroke or Systemic Embolism) in the PerProtocol Population and in the Intention-to-Treat Population.

Patel MR et al. N Engl J Med 2011;365:883-891

Rates of Bleeding Events.

Patel MR et al. N Engl J Med 2011;365:883-891

Conclusions

In patients with atrial fibrillation,

rivaroxaban was noninferior to warfarin

for the prevention of stroke or systemic
embolism.
There was no significant between-group
difference in the risk of major bleeding,
although intracranial and fatal bleeding
occurred less frequently in the
rivaroxaban group.

Original Article

Apixaban versus Warfarin in Patients with Atrial

Fibrillation (ARISTOTLE)
The oral direct factor Xa inhibitor, apixaban, was compared with
warfarin in atrial fibrillation.
Apixaban was superior to warfarin in preventing stroke or
systemic embolism, caused less bleeding, and lowered mortality.

N Engl J Med
Volume 365(11):981-992
September 15, 2011

KaplanMeier Curves for the Primary Efficacy and Safety Outcomes.

Granger CB et al. N Engl J Med 2011;365:981-992

Efficacy Outcomes.

Granger CB et al. N Engl J Med 2011;365:981-992

Bleeding Outcomes and Net Clinical Outcomes.

Granger CB et al. N Engl J Med 2011;365:981-992

Conclusions

In patients with atrial fibrillation,

apixaban was superior to warfarin in

preventing stroke or systemic embolism,
caused less bleeding, and resulted in
lower mortality.

rata NOAc

rata WAR

CI

AVC/TES

3,11%

3,79%

0,81(0,73-0,91)

AVC hemor

0,44%

0,90%

0,49(0,38-0,64)

Hemor maj

5,26%

6,17%

0,86(0,73-1)

HIC

0,70%

1,45%

0,48(0,39-0,59)

Mo generala 6,90%

7,68%

0,90(0,85-0,95)

J.Udell, Metaanaliza NOAC vs WAR,

2014

Excizia / inchiderea US

Tehnici
Chirurgical: in cursul interv cardiace
Minimal invazive: epicardice / trans SIA
WATCHMAN / AMPLATZER CARDIAC PLUG

Ratiuni: alternativa la ACO cronic

Limite:

Studii mici, putine, in curs

Nu toate AVC sint legate de FiA
Alte localizari posibile ale trombilor
Nu exista comparatii intre tehnicile neinvazive

Studii

PROTECT-AF:
WATCHMAN vs ACO
(707 PTS)
Complicatii precoce
postinterventionale

PREVAIL: WATCHMAN
vs WARFARINA CR (in
curs)

Terapia antiremodelare
miocardica si fibrilatia atriala

Terapia antiremodelare
intirzierea

remodelarii

Preventie I FiA
Preventie II FiA: ratei recurentelor/ progresiei FiA

Droguri cu valente antiremodelare

IEC / ARB
antialdosteronice
statine
AG polinesaturati (PUFA)

IEC/ARB in preventia I FiA

In IC:
riscului FiA cu 30-48% in HFREF
Nu exista evidente in HFPEF
In HTA rezultate neclare:

Studii HTA: LIFE (Lo), VALUE (Val) = (+)

Studii HTA + FR: HOPE (Ram), TRANSCEND
(Telmi) = (-)

IEC / ARB in preventia II FiA

1

metaanaliza: risc recurenta cu 4550%

in asociere cu AA

CAPRAF (Candesartan in preventia FiA

recurente: (-)
NB! fara AA
GISSI-AF: FiA paroxistica/perrsistenta

recurenta: Valsartan + AA + IEC: (-)

Antialdosteronicele in preventia
FiA
Haldosteronismul
FiA

sg.

primar risc x12 FiA

se asociaza cu nivel crescut aldost

Antialdosteronicele

rol neclar

Spironolactona: pare a recurenta FiA

postcardioversie la HTA & disfunctie VS

Statinele in preventia FiA

Mecanisme

posibile:

ameliorarea metabolism lipidic

antiaterosclerotic
antiinflamator & antioxidant
ameliorarea disfunctiei endoteliale
ameliorarea activarii NH

Statinele in preventia FiA

Preventia

I: doar studii obs,

retrospective
(+): in disfunctia VS si IC
(-): in HTA, ischemie

Preventia

II:

fara efecte certe

Postoperator:

3 studii - 17643 pac

incid I episod FiA (p<0,001)

efect dependent de doza