1. Adriana Gurghean Sibiu, august 2014
Fibrilatia atriala
Adriana Gurghean
Sibiu, august 2014

2. 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 !!!

4. Screening FiA 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

5. 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

6. 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

7. Mecanismele de aparitie a FiA
anomalii structurale V si A
disociatie intre fb mm si conducere electrica
circuite mici de reintrare
initiere
perpetuare
stabilitate

8. 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

9. 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

10. 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 ↑

11. 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

12. Evolutia naturala a FiA
AF = atrial fibrillation 12 12

13. Tipuri de FiA “ Lone AF’’ – fara o boala cardiaca structurala
FiA non-valvulara
absenta SMi, proteze valvulare, plastie VMi
FiA secundara
ex. infectii acute

14. Evaluarea clinica Evaluarea simptomelor (scorul EHRA)
Estimarea riscului de AVC
Dg conditiilor predispozante pt FiA
Evaluarea complicatiilor

15. 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)

16. Tratamentul FiA Ameliorarea simptomelor controlul ritmului
controlul frecventei
Prevenirea complicatiilor
tratamentul antitrombotic
Tratamentul conditiilor asociate
Urgenta !!! SEE sincron

17. 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 !

19. Conversia electrica a FiA
SEE sincron 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

20. DC cardioversion for AF
aClass of recommendation. bLevel of evidence.
AF = atrial fibrillation; DCC = direct current cardioversion. 20 20

21. 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. 21 21

22. 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

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

24. Vernakalant – reactii adverse si contraindicatii
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 %

26. Terapia antiaritmica orala
I: preventia FiA recurenta (persistenta / paroxistica)
!!Eficienta vs reactii adverse si Mo crescute
Controlul simptomelor persistente date de recurenta FiA

27. 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

28. Dronedarona in mentinerea RS
Structura asemanatoare A
Blocant multiplu:
canale Na si K
antiadrenergic
prop asemanatoare Ca blocantelor
Eficienta: superior placebo/ inferior A

29. Dronedarona - studii

30. Dronedarona – I si CI I: CI: 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

32. 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. 32 32

33. Concluzii – terapia AA orala pt controlul ritmului

34. Recurenta FiA la pacientii cu AAD

38. 77% - RFCA vs 19% - 52% - AAD !
Yun-Yu Chen, BS.
2013

39. 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

40. 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 ?

41. Ablatia pe cateter vs ablatia chirurgicala
Studiul FAST
A chirurgicala – eficienta > in controlul ritm
A chirurgicala - complicatii >
Dificultati tehnice

42. Ablatia chirurgicala ‘’maze procedure’’ Succes 75-95% la 15 ani
Complic si Mo crescute
FiA + BMi

43. Evaluarea preablatie Holter ECG Eco cord: afectare structurala
MRI, CT: fibroza A
TEE: excludere tromb AS, US
ACO preablatie

44. Controlul Frecventei in Fibrilatia Atriala

45. 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

46. Cind trebuie redusa frecventa ?
Terapia initiala
Pina la deciderea conversiei
Prevenirea frecventei inalte in FA paroxistica si persistenta recurenta
FA cronica

48. Cum alegem intre controlul frecventei si controlul ritmului in FiA persistenta ?

49. Quality of life
Morbidity
Mortality

51. 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

52. Factori ce influenteaza negativ mentinerea RS
Istoric indelungat de FiA
Virsta
Boala cardiovasculara severa coexistenta
Comorbiditati
AS dilatat

53. Cine ar beneficia cel mai mult de controlul frecventei ?

55. Controlul frecventei pe termen lung

56. Controlul frecventei pe termen lung

57. Care este frecventa optima ?
AFFIRM (60-80bpm rep; bpm effort moderat)
<110bpm, rep

59. Controlul nefarmacologic al frecventei
Ablatia nodului AV
paliativa, ireversibila
esecul terapiei farmacologice
Modificarea NAV – radiofrecventa
mai putin eficienta
Implantare PM fctie de tipul FiA (VVI, DDD, CRT)

60. Tratamentul antitrombotic in FiA

61. 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)

62. 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

63. 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

64. Scorul CHA2DS2 - VASc

65. 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

67. Terapia antitrombotica in FiA
Aspirina
Clopidogrel
Antivitamina K
Antitromboticele noi

68. 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 prefera dozele mici (<100mg)
FiA izolata – beneficiu mic / risc hemoragic mare (1,6% vs 0,4% placebo)

69. 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

70. 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

71. 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

73. Recomandarile pentru profilaxie

74. Anticoagularea pericardioversie

75. Anticoagularea pericardioversie

76. Anticoagularea, FiA si AVC acut

77. Anticoagularea, FiA si interventiile chirurgicale

78. Anticoagularea, FiA si stenturile

79. 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

80. Anticoagulantele noi
Inhibitori directi ai trombinei – dabigatran (RE-LY)
Inhibitori directi ai factorului Xa – rivaroxaban (ROCKET-AF) / apixaban (ARISTOTLE)

81. 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

82. Efficacy Outcomes, According to Treatment Group
Table 2. Efficacy Outcomes, According to Treatment Group.
Connolly SJ et al. N Engl J Med 2009;361:

83. Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group
Figure 1. 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:

84. Rata accidentelor hemoragice

85. 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

86. 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.

87. Primary End Point of Stroke or Systemic Embolism.
Table 2 Primary End Point of Stroke or Systemic Embolism.
Patel MR et al. N Engl J Med 2011;365:

88. Cumulative Rates of the Primary End Point (Stroke or Systemic Embolism) in the Per-Protocol Population and in the Intention-to-Treat Population.
Figure 1 Cumulative Rates of the Primary End Point (Stroke or Systemic Embolism) in the Per-Protocol Population and in the Intention-to-Treat Population.
Patel MR et al. N Engl J Med 2011;365:

89. Rates of Bleeding Events.
Table 3 Rates of Bleeding Events.
Patel MR et al. N Engl J Med 2011;365:

90. 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.

91. 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):
September 15, 2011

92. Kaplan–Meier Curves for the Primary Efficacy and Safety Outcomes.
Figure 1 Kaplan–Meier Curves for the Primary Efficacy and Safety Outcomes. The primary efficacy outcome (Panel A) was stroke or systemic embolism. The primary safety outcome (Panel B) was major bleeding, as defined according to the criteria of the International Society on Thrombosis and Haemostasis. The inset in each panel shows the same data on an enlarged segment of the y axis.
Granger CB et al. N Engl J Med 2011;365:

93. Efficacy Outcomes. Table 2 Efficacy Outcomes.
Granger CB et al. N Engl J Med 2011;365:

94. Bleeding Outcomes and Net Clinical Outcomes.
Table 3 Bleeding Outcomes and Net Clinical Outcomes.
Granger CB et al. N Engl J Med 2011;365:

95. 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.

96. 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

97. 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

98. Studii PROTECT-AF: WATCHMAN vs ACO (707 PTS)
Complicatii precoce postinterventionale
PREVAIL: WATCHMAN vs WARFARINA CR (in curs)

99. Terapia antiremodelare miocardica si fibrilatia atriala

100. 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)

101. 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) = (-)

102. IEC / ARB in preventia II FiA
1 metaanaliza: ↓risc recurenta cu 45-50%
in asociere cu AA
CAPRAF (Candesartan in preventia FiA recurente: (-)
NB! fara AA
GISSI-AF: FiA paroxistica/perrsistenta recurenta: Valsartan + AA + IEC: (-)

103. Antialdosteronicele in preventia FiA
Haldosteronismul primar – risc x12 FiA
FiA se asociaza cu nivel crescut aldost sg.
Antialdosteronicele – rol neclar
Spironolactona: pare a ↓recurenta FiA postcardioversie la HTA & disfunctie VS

104. Statinele in preventia FiA
Mecanisme posibile:
ameliorarea metabolism lipidic
antiaterosclerotic
antiinflamator & antioxidant
ameliorarea disfunctiei endoteliale
ameliorarea activarii NH

105. 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 pac
↓incid I episod FiA (p<0,001)
efect dependent de doza