Κολπική Μαρμαρυγή Παναγιώτης Γ. Κοραντζόπουλος Επίκουρος Καθηγητής Καρδιολογίας Παν. Ιωαννίνων
Mechanisms of Thrombus formation in AF Stasis Endothelial Dysfunction Hypercoaguble State (Virchow s triad) Impairs atrial contraction, and promotes blood stasis in the left atrium Systemic and atrial tissue levels of P selectin and Von Willebrand factor are elevated in some patients The plasma concentration of fibrinopeptide A, fibrin, D dimer is elevated and antithrombin III is decreased In AF, intracardiac thrombus in situ contains primarily fibrin and amorphous debris T.Watson, G. Lip. Lancet 2009
Platelet microparticles, soluble P selectin, β thromboglobulin Increased in AF (role of underlying comorbidities?) In vitro measures of platelet aggregation were not increased in AF T.Watson, G. Lip. Lancet 2009
Idiopathic AF Increased sp selectin and fibrinogen but not vwf compared to controls Lone AF (idiopathic age<60) Increased sp selectin but not fibrinogen or vwf compared to controls
Επισημάνσεις. Στους μηχανισμούς θρομβογένεσης στην κολπική μαρμαρυγή εμπλέκεται η κλασσική τριάδα του Virchow Η στάση του αίματος αποτελεί τον κυριότερο παράγοντα σχηματισμού θρόμβου Ο ρόλος των αιμοπεταλίων είναι αμφισβητήσιμος In situ θρόμβοι αποτελούνται κυρίως από ινική και άμορφα συντρίμματα (debris), δηλαδή αποτελούν λευκούς θρόμβους
ΚΛΙΝΙΚΟ ΠΕΡΙΣΤΑΤΙΚΟ (1) Άνδρας 77 ετών με μόνιμη κολπική μαρμαρυγή Συνοσηρότητες: Αρτηριακή υπέρταση Αρχική Φαρμ. Αγωγή: Irbesartan+Hydrochlorothiazide, Bisorolol 5mg/d, Aspirin 100 mg/d Κάτοικος απομακρυσμένης ορεινής περιοχής Περιποιείται την κατάκοιτη σύζυγο Χαμηλού κοινωνικο οικονομικού προφίλ (μηνιαία σύνταξη 320 ) Προστέθηκε στην αγωγή Clopidogrel 75 mg x 1
Ασπιρίνη Κολπική Μαρμαρυγή
Κουμαρινικά vs Ασπιρίνη
ACTIVE-W W Trial Non-inferiority; open; clopidogrel 75mg + 150-200mg ASA vs. adjusted dose OAC; n=6706 Patients with AF and at least a moderate risk for stroke Primary outcome: combined stroke, peripheral embolism, myocardial infarction, vascular death Lancet 2006;367:1903 12
Primary end point: stroke, embolic event, MI, vascular death Πρώιμη διακοπή στον 1.5 χρόνο ΣαφήςΥπεροχήWarfarin Lancet 2006;367:1903 12
ACTIVE-W W Results Stopped early because OAC clearly superior Primary Outcome Annual Event Rate, % ASA+Clopido. OAC RRR 5.6 3.9 30% <0.01 Isch. Stroke 2.15 1.0(!) 53% <0.01 MI 0.86 0.55 36% 0.09 Major bleed 2.4 2.2 8.6% 0.5 p Lancet 2006;367:1903 12
ACTIVE A STUDY
ACTIVE A 7554 patients with A.F. who had an increased risk of stroke and for whom vitamin K antagonist therapy was unsuitable Randomization clopidogrel (75 mg) or placebo,once daily, in addition to aspirin.
ACTIVE A Primary outcome was the composite of stroke, myocardial infarction, non central nervous system systemic embolism, or death from vascular causes Secondary outcomes: stroke, hemorrhages Median F/U of 3.6 years
Relative Risks of Primary and Secondary Outcomes, According to Treatment Group The ACTIVE Investigators. N Engl J Med 2009;360:2066-2078
Cumulative Incidence of Trial Outcomes, According to Treatment Group The ACTIVE Investigators. N Engl J Med 2009;360:2066-2078
Cumulative Hazard Rates 0.0 0.05 0.10 0.15 HR=0.72 (0.62-0.83) p=0.00002 Placebo+Aspirin Clopidogrel+Aspirin 0 1 2 3 4 No. at Risk C+A 3772 3491 3229 2570 1203 ASA 3782 3458 3155 2517 1186 Years Graph courtesy of the ACTIVE group
Relative Risks of Hemorrhage, According to Treatment Group The ACTIVE Investigators. N Engl J Med 2009;360:2066-2078
ΑΝΤΙΘΡΟΜΒΩΤΙΚΗ ΑΓΩΓΗ ΣΤΗΝ ΚΟΛΠΙΚΗ ΜΑΡΜΑΡΥΓΗ
ΜΠΟΡΟΥΜΕ ΝΑ ΑΠΟΦΥΓΟΥΜΕ ΕΝΤΕΛΩΣ ΤΗΝ ΑΝΤΙΘΡΟΜΒΩΤΙΚΗ ΑΓΩΓΗ ΣΤΗΝ ΚΟΛΠΙΚΗ ΜΑΡΜΑΡΥΓΗ? Παραδείγματα ασθενών Ασθενής που έχει υποστεί σοβαρή ή απειλητική για τη ζωή αιμορραγία ή υποτροπιάζουσες αιμορραγίες / πολύ υψηλό HASBLED score Aσθενής με σοβαρή αναιμία/ αιματολογικό νόσημα / αιμορραγική
ΕΠΕΜΒΑΤΙΚΗ ΣΥΓΚΛΙΣΗ Ή ΣΥΡΡΑΦΗ ΩΤΙΟΥ ΑΡΙΣΤΕΡΟΥ ΚΟΛΠΟΥ
The procedure was successful in 98.1% of the patients, and the main complications were device embolization (1.9%) and pericardial effusion (1.9%), with no cases of periprocedural stroke. At a mean follow up of 20±5 months, the rates of death, stroke, systemic embolism, pericardial effusion, and major bleeding were 5.8%, 1.9%, 0%, 1.9%, and 1.9%, respectively. Antiplatelet therapy consisting of aspirin (80 to 325 mg/24 h) plus clopidogrel (75 mg/24 h), or aspirin or clopidogrel alone was given according to the operators discretion for 30 to 180 days after the procedure, after which single antiplatelet therapy was given.
Eighty five (96%) of 89 patients underwent successful LAA ligation. Eighty one of 85 patients had complete closure immediately. Three of 85 patients had a 2 mm residual LAA leak by TEE color Doppler evaluation. One of 85 patients had a 3 mm jet by TEE. There were no complications due to the device. There were 3 access related complications (during pericardial access, n 2; and transseptal catheterization, n 1). Adverse events included severe pericarditis post operatively (n 2), late pericardial effusion (n 1), unexplained sudden death (n 2), and late strokes thought to be nonembolic (n 2). At 1 month (81 of 85) and 3 months (77 of 81) post ligation, 95% of the patients had complete LAA closure by TEE. Of the patients undergoing 1 year TEE (n 65), there was 98% complete LAA closure, including the patients with previous leaks.