Fibrilatia atriala
Adriana Gurghean
Sibiu, august 2014
Date epidemiologice
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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
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EMBRACE & CRYSTAL-AF - > 1000 pac
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
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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
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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
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Focare anormale
mec celulare: automatism / reintrare
v pulm (FiA parox) / dispersate (FiA persist)
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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
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EF: ↓PRE : primele zile
down-reglarea curenti Ca tip L
up-reglarea curenti rectificatori de K
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Mecanic: contractilitate ineficienta: zile
down-reglarea curentilor de Ca
scaderea eliberarii Ca din depozite
modificarea prop energetice miofibrilare
Principalele consecinte clinice
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Alterarea hemodinamicii
pierderea contractiei atriale
frecventa V crescuta, neregulata
scaderea fluxului miocardic
cardiomiopatia A si V
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Accidentele tromboembolice
anomalii ale fluxului: staza AS si US
anomalii ale componentelor sg: activare
plachetara, hemostaza, inflamatie, factori de ↑
Clasificarea FiA
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1. Primul episod de FiA – indiferent de durata /
severitatea simptomelor
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2. FiA paroxistica – max 48 h
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3. FiA persistenta - > 7 zile / necesita cardioversie
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4. FiA persistenta lunga - > 1 an
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5. FiA permanenta – acceptata de pacient/dr **
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FiA asimptomatica – oricare din cele 5 forme/dg ocazional
sau printr-o complicatie
Evolutia naturala a FiA
AF = atrial fibrillation
Tipuri de FiA
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“ Lone AF’’ – fara o boala cardiaca structurala
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FiA non-valvulara
– absenta SMi, proteze valvulare, plastie VMi
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FiA secundara
– ex. infectii acute
Evaluarea clinica
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Evaluarea simptomelor (scorul EHRA)
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Estimarea riscului de AVC
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Dg conditiilor predispozante pt FiA
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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
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Ameliorarea simptomelor
controlul ritmului
controlul frecventei
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Prevenirea complicatiilor
tratamentul antitrombotic
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Tratamentul conditiilor asociate
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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
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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
aClass
of recommendation. bLevel of evidence.
AF = atrial fibrillation; DCC = direct current cardioversion.
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
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Reactii adverse
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Hipotensiune arteriala 5-7% (16% in IC)
Bradicardie 0,5%
TR-V – in IC 7,3% TVNS
Alungirea QT si QRS
Contraindicatii
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TAs < 100 mmHg
SCA < 30 zile
IC NYHA III-IV
SAO severa
QT > 440msec
FE < 35 %
Terapia antiaritmica orala
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I: preventia FiA recurenta (persistenta /
paroxistica)
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!!Eficienta vs reactii adverse si Mo
crescute
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Controlul simptomelor persistente date de
recurenta FiA
Antiaritmicele orale – pe ce durata ?
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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
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Amiodarona
– Long (t1/2 lung)
– Short (episodic) daca: r adv sint mici sau
recurentele sint rare
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Dronedarona
Dronedarona in mentinerea RS
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Structura asemanatoare A
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Blocant multiplu:
– canale Na si K
– antiadrenergic
– prop asemanatoare Ca blocantelor
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Eficienta: superior placebo/ inferior A
Dronedarona - studii
Dronedarona – I si CI
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I:
– FiA paroxistica / persistenta post conv.
– IC NYHA I –II cu FE pastrata
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CI:
– FiA permanenta (PALLAS)
– IC NYHA III-IV (ANDROMEDA)
– Instabilitate hemodinamica
– Disfunctie sistolica VS
Choice of an antiarrhythmic drug
for AF control
aClass
of recommendation. bLevel of evidence.
AF = atrial fibrillation; AV = atrioventricular; LoE = level of evidence; NYHA = New York Heart Association.
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
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Limite ale eficacitatii
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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
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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
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Studiul FAST
– A chirurgicala – eficienta > in controlul ritm
– A chirurgicala - complicatii >
– Dificultati tehnice
Ablatia chirurgicala
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‘’maze procedure’’
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Succes 75-95% la 15 ani
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Complic si Mo crescute
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FiA + BMi
Evaluarea preablatie
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Holter ECG
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Eco cord: afectare structurala
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MRI, CT: fibroza A
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TEE: excludere tromb AS, US
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ACO preablatie
Controlul Frecventei in
Fibrilatia Atriala
Efectele functionale ale FiA
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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
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Insuficienta cardiaca
Cind trebuie redusa frecventa ?
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Terapia initiala
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Pina la deciderea conversiei
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Prevenirea frecventei inalte in FA
paroxistica si persistenta recurenta
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FA cronica
Cum alegem intre controlul frecventei si controlul ritmului in FiA persistenta ?
Quality of
life
Morbidity
Mortality
Controlul ritmului vs controlul
frecventei
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Impactul FiA cronice asupra evolutiei
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Probabilitatea de mentinere a RS
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Severitatea simptomatologiei legate de FiA
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Factori ce pot influenta mentinerea RS
Factori ce influenteaza negativ
mentinerea RS
Istoric indelungat de FiA
 Virsta
 Boala cardiovasculara severa coexistenta
 Comorbiditati
 AS dilatat
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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
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Ablatia nodului AV
– paliativa, ireversibila
– esecul terapiei farmacologice
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Modificarea NAV – radiofrecventa
– mai putin eficienta
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Implantare PM fctie de tipul FiA (VVI,
DDD, CRT)
Tratamentul antitrombotic in
FiA
Factorii de risc tromboembolic in FiA
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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
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Categoriile de risc – mai degraba artificiale
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Beneficii ACO vs aspirina si la cei cu risc moderat
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Nu include multi alti FR-TE
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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
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Aspirina
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Clopidogrel
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Antivitamina K
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Antitromboticele noi
Aspirina in FiA
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Metaanaliza 8 studii (4876 pts)
– reducerea RA cu 0,8%/an – prev I
– reducerea RA cu 2,5%/an – prev II
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Se prefera dozele mici (<100mg)
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FiA izolata – beneficiu mic / risc hemoragic
mare (1,6% vs 0,4% placebo)
Aspirina + Clopidogrel in FiA
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ACTIVE-W: CLO+ASA vs WAR
– WAR superioara (reducere RR AVC isch cu 40%)
– WAR – acelasi risc hemoragic
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ACTIVE-A: CLO+ASA vs ASA
– CLO+ASA superior / risc hemoragic mare
Concluzii: CLO+ASA doar daca ACO e CI
Antivitamine K in FiA
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Reducerea RR AVC ischemic cu 67%
– INR terapeutic
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Rezultate similare pentru preventia I si II
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Reducere Mo generala cu 26%
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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
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Anticoagulantele noi
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Inhibitori directi ai trombinei – dabigatran (RE-LY)
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Inhibitori directi ai factorului Xa – rivaroxaban
(ROCKET-AF) / apixaban (ARISTOTLE)
Dabigatran versus Warfarin in Patients with Atrial
Fibrillation (RE-LY)
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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)
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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
Kaplan–Meier 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
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Tehnici
– Chirurgical: in cursul interv cardiace
– Minimal invazive: epicardice / trans SIA
WATCHMAN / AMPLATZER CARDIAC PLUG
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Ratiuni: alternativa la ACO cronic
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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
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PROTECT-AF:
WATCHMAN vs ACO
(707 PTS)
– Complicatii precoce
postinterventionale
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PREVAIL: WATCHMAN
vs WARFARINA CR (in
curs)
Terapia antiremodelare miocardica
si fibrilatia atriala
Terapia antiremodelare
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intirzierea remodelarii
 Preventie I FiA
 Preventie II FiA: ↓ratei recurentelor/ progresiei FiA
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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
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In HTA – rezultate neclare:
– Studii HTA: LIFE (Lo), VALUE (Val) = (+)
– Studii HTA + FR: HOPE (Ram), TRANSCEND
(Telmi) = (-)
IEC / ARB in preventia II FiA
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1 metaanaliza: ↓risc recurenta cu 45-50%
– in asociere cu AA
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CAPRAF (Candesartan in preventia FiA
recurente: (-)
– NB! fara AA
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GISSI-AF: FiA paroxistica/perrsistenta
recurenta: Valsartan + AA + IEC: (-)
Antialdosteronicele in preventia FiA
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Haldosteronismul primar – risc x12 FiA
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FiA se asociaza cu nivel crescut aldost sg.
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Antialdosteronicele – rol neclar
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Spironolactona: pare a ↓recurenta FiA
postcardioversie la HTA & disfunctie VS
Statinele in preventia FiA
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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