Fibrilatia atrialaAdriana GurgheanSibiu, august 2014

Date epidemiologice1,5-2% populatia generala5-15% la varstnici1/20 AVC acuteriscul de aparitie a FiA > 40 ani = 25%mai frecventa la barbatirisc de AVC de 5x mai mare; frecvent fatalrisc de IC de 3x mai mare !!!

Screening FiAEMBRACE & CRYSTAL-AF - > 1000 pac

pac cu AVC criptogenetic monitorizati prelungit: 1luna / monitor implantabil au evidentiat episoade de FiA de 5x mai frecvente fata de martorNEJM, june 2014

Riscul de evenimente cardiovasculareDeces cardiovascular dubluInsuficienta cardiaca 30-40% si inversCM tahiaritmicaAVC acelasi risc pentru toate formele de FiASpitalizari frecvente 1/3 spitalizarile pentru TRDisfunctie VS asimptomaticaToleranta redusa la effortScaderea calitatii vietii

Asocieri frecvente cu FiAVarstaInsuficienta cardiacaValvulopatii degenerativeCardiomiopatiiBoli congenitale DSA 10-15%Ischemia miocardica 20% FiADistiroidiiObezitate 25% din FiADiabet 20% din FiABPOC 10-15% din FiASleep-apnoea BCR 10-15% din Fia

Mecanismele de aparitie a FiAdisociatie intre fb mm si conducere electricaanomalii structurale V si Acircuite mici de reintrareinitiereperpetuarestabilitate

Mecanismele electrofiziologice si predispozitia geneticaFocare anormalemec celulare: automatism / reintrarev pulm (FiA parox) / dispersate (FiA persist)

Unde multipleconducere continua, haotica, independenta

Predispozitia genetica- sdr QT lung / scurt; preexcitatie V- CMH- mutatii gene: ANP, hipofct can Na, Hfct can K

Consecintele fiziopatologice ale FiAEF: PRE : primele ziledown-reglarea curenti Ca tip Lup-reglarea curenti rectificatori de K

Mecanic: contractilitate ineficienta: ziledown-reglarea curentilor de Cascaderea eliberarii Ca din depozitemodificarea prop energetice miofibrilare

Principalele consecinte cliniceAlterarea hemodinamiciipierderea contractiei atrialefrecventa V crescuta, neregulatascaderea fluxului miocardiccardiomiopatia A si V

Accidentele tromboemboliceanomalii ale fluxului: staza AS si USanomalii ale componentelor sg: activare plachetara, hemostaza, inflamatie, factori de

Clasificarea FiA1. 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 FiAAF = atrial fibrillation

Tipuri de FiA Lone AF fara o boala cardiaca structurala

FiA non-valvularaabsenta SMi, proteze valvulare, plastie VMi

FiA secundaraex. infectii acute

Evaluarea clinicaEvaluarea simptomelor (scorul EHRA)

Estimarea riscului de AVC

Dg conditiilor predispozante pt FiA

Evaluarea complicatiilor

Evaluarea clinica initialaMomentul instalarii FiA tip FiASemne de IC acutacontrol urgent AVcardioversieeco fct VS, PsVD, valveAIT / AVC CT +/- revascularizareEvaluare risc AVC: ACOEvaluarea cauzeloreco cordfctie tiroidaHLG, creat, glicemieteste stress pt ischemiecoronarografie (persist disf)

Tratamentul FiAAmeliorarea simptomelorcontrolul ritmuluicontrolul frecventei

Prevenirea complicatiilortratamentul antitrombotic

Tratamentul conditiilor asociate

Urgenta !!! SEE sincron

Controlul ritmului in FiACardioversia farmacologica sau electrica a FiA persistente sau supresia episoadelor recurente de FiA paroxistica

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

Conversia electrica a FiASEE sincron 200-360 JSedare / midazolamIn urgenta : simpt severe / degradare hemodinamica / WPWElectiva : stabiliACO 3 sapt antFiA< 48 h - control TEE si conversie+/- pretratament AA

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

Drugs and doses for pharmacologicalconversion of (recent-onset) AFACS = 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 farmacologicaVernakalant

FiA < 7 zile / < 3 zile postinterv cardiaceActiune: atrialPrelungeste PRA si scade conducerea AInstalare efect: rapidaT1/2 = 3-5 ore

Vernakalant - studiiSuperior AmiodaronaEficient la: HTAIschemiepostoperator+/-: ICIneficient in: FiA > 7 zile/ FlA tipic

Vernakalant reactii adverse si contraindicatiiReactii adverseHipotensiune arteriala 5-7% (16% in IC)Bradicardie 0,5%TR-V in IC 7,3% TVNSAlungirea QT si QRS

ContraindicatiiTAs < 100 mmHgSCA < 30 zileIC NYHA III-IVSAO severaQT > 440msecFE < 35 %

Terapia antiaritmica oralaI: preventia FiA recurenta (persistenta / paroxistica)

!!Eficienta vs reactii adverse si Mo crescute

Controlul 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); longShort: protectie 80% long la 6 lAmiodaronaLong (t1/2 lung)Short (episodic) daca: r adv sint mici sau recurentele sint rareDronedarona

Dronedarona in mentinerea RSStructura asemanatoare A

Blocant multiplu:canale Na si Kantiadrenergicprop asemanatoare Ca blocantelor

Eficienta: superior placebo/ inferior A

Dronedarona - studii

Dronedarona I si CII: FiA paroxistica / persistenta post conv.IC NYHA I II cu FE pastrataCI:FiA permanenta (PALLAS)IC NYHA III-IV (ANDROMEDA)Instabilitate hemodinamicaDisfunctie sistolica VS

Choice of an antiarrhythmic drugfor AF controlaClass 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 Limite ale eficacitatii

FiA persistenta lunga (>1 an)AS dilatat (>55 mm)Age > 70 yearsPatologie structurala cardiaca Recurente mai frecvente pe termen lung

Complicatii

TC, pericardita, fistula A-E, stenoza VPVasculare perifericeInfarct cerebral silentios (MRI) 4-35%*

Ablatia in FiA cu ICEficienta neclara in IC cu disfunctie VSAmiodarona e I indicatieI: simptome legate de FiA sub amiodaronaACO = obligatorieRata mentinerii RS e micaRiscurile procedurale mult mai mariAmeliorarea functiei VS ?

Ablatia pe cateter vs ablatia chirurgicalaStudiul FAST

A chirurgicala eficienta > in controlul ritmA chirurgicala - complicatii >Dificultati tehnice

Ablatia chirurgicalamaze procedure

Succes 75-95% la 15 ani

Complic si Mo crescute

FiA + BMi

Evaluarea preablatieHolter ECG

Eco cord: afectare structurala

MRI, CT: fibroza A

TEE: excludere tromb AS, US

ACO preablatie

Controlul Frecventei in Fibrilatia Atriala

Efectele functionale ale FiAPierderea pompei atrialeIn caz de HVS reducerea volumului bataie cu peste 25 %Scurtarea diastolei umplere deficitaraTahicardia de efort simptome de efort Miocardiopatia tahicardica

Insuficienta cardiaca

Cind trebuie redusa frecventa ?Terapia initiala

Pina la deciderea conversiei

Prevenirea frecventei inalte in FA paroxistica si persistenta recurenta

FA cronica

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

Quality of lifeMorbidityMortality

Controlul ritmului vs controlul frecventeiImpactul 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 RSIstoric indelungat de FiAVirstaBoala cardiovasculara severa coexistentaComorbiditatiAS dilatat

Cine ar beneficia cel mai mult de controlul frecventei ?

Controlul frecventei pe termen lung

Controlul frecventei pe termen lung

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

Controlul nefarmacologic al frecventeiAblatia nodului AVpaliativa, ireversibilaesecul terapiei farmacologice

Modificarea NAV radiofrecventamai putin eficienta

Implantare PM fctie de tipul FiA (VVI, DDD, CRT)

Tratamentul antitrombotic in FiA

Factorii de risc tromboembolic in FiAAntecedente de accidente TEVarstaDiabet zaharatHTABoli structurale cardiaceDisfunctia 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)Scor 0 = risc micScor 1-2 = risc moderatScor > 2 = risc crescut>2 = ACO cronic2 = istoric AVC / AIT1 = varsta > 75 aniHTAICDZ

Limitele scorului CHADS2Categoriile 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 hemoragicHEMORR2 HAGESHepatic or renal disease, Ethanol abuse, Malignancy, Older (>75), reduced platelet count/function, Rebleeding risk, Hypertension, Anemia, Genetic factors, Excessive fall risk, StrokeHAS-BLEDHypertension, Abnormal liver/renal function, Stroke, Bleeding history, Labile INR, Elderly, Drugs/alcoholATRIAAnTicoagulation and Risk factors In Atrial fibrillation

Terapia antitrombotica in FiAAspirina

Clopidogrel

Antivitamina K

Antitromboticele noi

Aspirina in FiAMetaanaliza 8 studii (4876 pts)reducerea RA cu 0,8%/an prev Ireducerea RA cu 2,5%/an prev II

Se prefera dozele mici (

Aspirina + Clopidogrel in FiAACTIVE-W: CLO+ASA vs WARWAR superioara (reducere RR AVC isch cu 40%)WAR acelasi risc hemoragic

ACTIVE-A: CLO+ASA vs ASACLO+ASA superior / risc hemoragic mare

Concluzii: CLO+ASA doar daca ACO e CI

Antivitamine K in FiAReducerea 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 periablatiePrevine TES indiferent de FRNu se intrerupe/se scade daca e nevoieE recomandata postablatie pe termen lung la scor > 2.ACO noi nu exista experienta

Anticoagulantele noiInhibitori directi ai trombinei dabigatran (RE-LY)

Inhibitori directi ai factorului Xa rivaroxaban (ROCKET-AF) / apixaban (ARISTOTLE)

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

Dabigatran versus Warfarin in Patients with Atrial Fibrillation (RE-LY)

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

Rata accidentelor hemoragice

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 hemorrhageDabigatran 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 hemorrhageConclusion

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 Per-Protocol 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

ConclusionsIn 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)N Engl J MedVolume 365(11):981-992September 15, 2011The 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.

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

ConclusionsIn patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.

rata NOAcrata WARCI

AVC/TES3,11%3,79%0,81(0,73-0,91)

AVC hemor0,44%0,90%0,49(0,38-0,64)

Hemor maj5,26%6,17%0,86(0,73-1)

HIC0,70%1,45%0,48(0,39-0,59)

Mo generala6,90%7,68%0,90(0,85-0,95)

J.Udell, Metaanaliza NOAC vs WAR, 2014

Excizia / inchiderea USTehniciChirurgical: in cursul interv cardiaceMinimal invazive: epicardice / trans SIAWATCHMAN / AMPLATZER CARDIAC PLUG

Ratiuni: alternativa la ACO cronic

Limite: Studii mici, putine, in cursNu toate AVC sint legate de FiAAlte localizari posibile ale trombilorNu 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 antiremodelareintirzierea remodelarii Preventie I FiAPreventie II FiA: ratei recurentelor/ progresiei FiADroguri cu valente antiremodelareIEC / ARBantialdosteronicestatineAG polinesaturati (PUFA)

IEC/ARB in preventia I FiAIn 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 FiA1 metaanaliza: risc recurenta cu 45-50%in asociere cu AACAPRAF (Candesartan in preventia FiA recurente: (-) NB! fara AAGISSI-AF: FiA paroxistica/perrsistenta recurenta: Valsartan + AA + IEC: (-)

Antialdosteronicele in preventia FiAHaldosteronismul 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

Statinele in preventia FiAMecanisme posibile:

ameliorarea metabolism lipidicantiateroscleroticantiinflamator & antioxidantameliorarea disfunctiei endotelialeameliorarea activarii NH

Statinele in preventia FiAPreventia I: doar studii obs, retrospective(+): in disfunctia VS si IC(-): in HTA, ischemiePreventia II:fara efecte certePostoperator: 3 studii - 17643 pacincid I episod FiA (p

********Table 2. Efficacy Outcomes, According to Treatment Group.Figure 1. Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group.Table 2 Primary End Point of Stroke or Systemic Embolism.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.Table 3 Rates of Bleeding Events.Figure 1 KaplanMeier 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.Table 2 Efficacy Outcomes.Table 3 Bleeding Outcomes and Net Clinical Outcomes.