1、john d. hummel, md ohio state university medical center ross heart hospital columbus, ohio management of atrial fibrillation in 2010 learning objectives understand the risk factors for atrial fibrillation. understand the guidelines for anticoagulation and where there is latitude for physician decisi

2、on making. be able to determine when patients should be evaluated for curative ablation. atrial fibrillation easily recognized. seems to bother healthcare workers as much as patients. whos problem? internists cardiologists ep. go a, et al. jama. 2001;285:2370-2375. projected number of adults with af

3、 in the us: 1995 to 2050. atrial fibrillation: costs to the health care system 35% of arrhythmia hospitalizations average hospital stay = 5 days mean cost of hospitalization = $18,800 does not include: costs of outpatient cardioversions costs of drugs/side effects/monitoring costs of af-induced stro

4、kes estimated us cost burden 15.7 billion alot! paroxysmal (self-terminating) first detected permanent classification of atrial fibrillation acc/aha/esc guidelines persistent (not self-terminating) diagnostic workup identify causes and risk factors minimum evaluation history and physical bp, cv dz e

5、lectrocardiogram wpw, lvh, mi echocardiogram lvh, lae, ef, valve dz labs tsh, renal fxn, lfts (clearance,etoh) d-dimer, esr additional testing ett cad, exercise induced svt / af holter / event monitor confirm af and sxs tee la clot cxr eps svt triggered af aha / acc / ecs guidelines 2006 20 15 10 5

6、0 years cumulative frequency of af (%) osa gami, et al. jacc 2007;49:565-71 cumulative frequency curves for incident atrial fibrillation (af) for subjects 2 mitral stenosismoderate-risk factors prosthetic heart valvecoumadin inr 2-3 moderate-risk factors(mechanical valve inr 2.5) age 75 yrs htn1 mod

7、erate-risk factor chfasa or coumadin dm ef or =0.5 microg/ml) in 63 (23%) patients. during an average follow-up period of 756 +/- 221 days: 1. 10 (1.8%/year) thromboembolic events (8 ischemic strokes, 1 transient ischemic attack, and 1 peripheral embolism 2. 27 (4.8%/year) combined cardiovascular ev

8、ents (10 thromboembolisms, 9 deaths from heart failure, 3 sudden deaths, 2 myocardial infarctions, and 3 cerebral hemorrhages) patients with elevated d-dimer levels experienced higher thromboembolic and combined cardiovascular events. sadanaga t, et. al; j am coll cardiol. 2010 may 18;55(20):2225-3.

9、 dabigatran vs. warfarin noninferiority trial randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive: 1. fixed doses of dabigatran 110 mg or 150 mg twice daily in a blinded fashion 2. adjusted-dose warfarin in an unblinded fashion the median duration of the fol

10、low-up period was 2.0 years. the primary outcome was stroke or systemic embolism. results primary outcome 1.69% per year in the warfarin group 1.53% per year in the group that received 110 mg of dabigatran (p0.001 for noninferiority) 1.11% per year in the group that received 150 mg of dabigatran ( p

11、0.001 for superiority) major bleeding 3.36% per year in the warfarin group 2.71% per year in the group receiving 110 mg of dabigatran (p=0.003) 3.11% per year in the group receiving 150 mg of dabigatran (p=0.31). hemorrhagic stroke 0.38% per year in the warfarin group 0.12% per year with 110 mg of d

12、abigatran (p0.001) 0.10% per year with 150 mg of dabigatran (p0.001). mortality rate 4.13% per year in the warfarin group 3.75% per year with 110 mg of dabigatran (p=0.13) 3.64% per year with 150 mg of dabigatran (p=0.051). conclusions dabigatran 110 mg had rates of stroke and systemic embolism simi

13、lar to warfarin with less major hemorrhage. dabigatran 150 mg had lower rates of stroke and systemic embolism but similar rates of major hemorrhage. stuart j. connolly and the re-ly steering committee and investigators nejm sept 17, 2009, no. 12, vol 361: 1139-1151 af therapy antithrombotic rx rhyth

14、m control rate control or ? and the affirm investigators. n engl j med. 2002;347:1825-1833. affirm trial: rate vs rhythm control management strategy trial design 5-year, randomized, parallel-group study comparing rate control vs. aarx attempt at nsr primary endpoint: overall mortality patient popula

15、tion 4060 patients with af and risk factors for stroke minimal symptoms mean age = 69 yo hx of hypertension: 70.8% cad: 38.2% enlarged la: 64.7% depressed ef: 26.0% affirm: all-cause mortality rate n: rhythm n: 2027 2033 1925 1932 1825 1807 1328 1316 774 780 236 255 0 5 10 15 20 25 30 012345 mortali

16、ty, % rate rhythm p=0.078 unadjusted time (years) p=0.068 adjusted the affirm investigators. n engl j med. 2002;347:1825-1833. raterhythm ischemic stroke 77 (5.5%)* 80 (7.1%)* inr 2.027 (35%)17 (21%) not taking warfarin 25 (32%)44 (55%) * p=0.79 the affirm investigators. n engl j med. 2002;347:1825-

17、1833. affirm: adverse events 100 80 60 40 20 0 time (years) percent with af recurrence rate control raitt, et al. am h j 2006 0123456 n, events (%) rate control: rhythm control: 563, 3 (0) 729, 2 (0) 167, 383 (69) 344, 356 (50) 98, 440 (80) 250, 422 (60) 42, 472 (87) 143, 470 (69) 10, 481 (92) 73, 4

18、94 (75) 2, 484 (95) 18, 503 (79) time to first recurrence of af. time 0 is the day of randomization rhythm control log rank statistic = 58.62 p 0.0001 implications affirm has demonstrated that rate control is an acceptable primary therapy in a selected high-risk subgroup of af patients with minimal

19、symptoms continuous anticoagulation seems warranted in all patients with risk factors for stroke asymptomatic recurrences atrial fibrillation: why control rate? rate control the problem: increased rates more symptomatic, greater hemodynamic impact. persistent increased rates tachycardia induced card

20、iomyopathy rate control the goal: paf control symptomatic tachycardia chronic afib mean 24hr hr 80-90 bpm (?) race ii hypothesis: lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in pts with permanent afib randomly assigned 614 patient

21、s with permanent af to: lenient rate-control strategy (resting heart rate 110 beats per minute) strict rate-control strategy (resting heart rate 80 beats per minute and heart rate during moderate exercise 110 beats per minute). primary outcome was a composite of death from cardiovascular causes, hos

22、pitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. the duration of follow-up was at least 2 years, with a maximum of 3 years. results: primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group

23、. (90% confidence interval, 7.6 to 3.5; p0.001 for the prespecified noninferiority margin). the frequencies of the components of the primary outcome were similar in the two groups. more patients in the lenient-control group met the heart-rate target or targets 97.7% vs. 67.0% in the strict-control g

24、roup; p0.001 with fewer total visits (75 vs. 684; p0.001). the frequencies of symptoms and adverse events were similar in the two groups. conclusions: in patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. van gelder, et.

25、al, for the race ii investigators nejm april 15, 2010, no. 15, vol 362: 1363-1373 atrial fibrillation rate control drug therapy: digoxin controls resting rate, ok in chf patients . beta, ca+2 blockers controls resting and exercise rates. best therapy combination of beta blocker and digoxin. even in

26、the best of circumstances pacing support is sometimes required goal: chronic afib mean 24hr hr 80-90 bpm (?) rate control plus anticoagulation preferred rhythm control preferred no or lesser af symptoms longer af hx more shd toxicity risk elderly greater risk of proarrhythmia greater af symptoms sym

27、ptoms despite rate control younger age no or lesser shd rx option of class ic aad in anticoagulation candidates, continue anticoagulation indefinitely approaches to af therapy atrial fibrillation duration of af is the best predictor of recurrent af after cardioversion dittrich hc. am j cardiol. 1989

28、;63:193-197. 12 months 100 80 60 40 20 0 initialone month post-cv six months post-cv *p = 6 months organ toxicity examples: lupus, agranulocytosis, thrombocytopenia, optic neuritis, pulmonary fibrosis, hepatitis, etc. negligible: dofetilide, flecainide, propafenone, sotalol, dronedarone acceptable:

29、azimilide, disopyramide high: amiodarone, procainamide, quinidine drug-induced proarrhythmia - torsades factors which influence ventricular proarrhythmia risk hypokalemia, hypomagnesemia long qt at baseline chf / decreased ef / ventricular hypertrophy bradycardia female gender reduced drug metabolis

30、m or clearance amiodarone and dronedarone has lowest risk (drondedarone cannot be started if baseline qtc/=500) aarx choice heart diseaseantiarrhythmic noneic or dronedarone vagal afibdisopyramide htnic (if no sig. lvh) then dronedarone cadsotalol chf/substantialamiodarone lvh prevention of atrial f

31、ibrillation by renin- angiotensin system inhibition schneider mp, et. al. j am coll cardiol. 2010 may 25;55(21):2299-307 meta analysis of published clinical trial data on the effects of renin-angiotensin system (ras) inhibition for the prevention of atrial fibrillation a total of 23 randomized contr

32、olled trials with 87,048 patients were analyzed. in primary prevention: 6 trials in hypertension, 2 trials in myocardial infarction, and 3 trials in heart failure were included. in secondary prevention: 8 trials after cardioversion and 4 trials assessing the medical prevention of recurrence were inc

33、luded. overall, ras inhibition reduced the odds ratio for af by 33% (p 0.00001), but there was substantial heterogeneity among trials. in primary prevention: ras inhibition was effective in patients with heart failure and those with hypertension and left ventricular hypertrophy but not in post-myoca

34、rdial infarction patients overall. in secondary prevention: ras inhibition was often administered in addition to antiarrhythmic drugs, including amiodarone, further reducing the odds for af recurrence after cardioversion by 45% (p = 0.01) and in patients on medical therapy by 63% (p 0.00001). ras in

35、hibition is an emerging treatment for the primary and secondary prevention of af alternatives to drug therapy “non-pharmacologic therapy” qcoumadin laa closure (watchman) qrate control avn rfa + pcmk qaarx adjunctive afl rfa qaarx curative afib rfa watchman laa filter system complete avn ablation avn