2011房颤治疗进展.ppt

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 FibrillationACC/AHA/ESC Guidelines,Persistent(Not self-terminating),DIAGNOSTIC WORKUPIdentify Causes and Risk Factors,Minimum Evaluation History and physical BP, CV dz Elect

5、rocardiogram 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 0 ,Y

6、ears,Cumulative Frequency of AF (%),OSA,Gami, et al. JACC 2007;49:565-71,Cumulative frequency curves for incident atrial fibrillation (AF) for subjects 65 years of age with and without obstructive sleep apnea (OSA) during an average 4.7 years of follow-up. p = 0.002,Number at Risk OSA No OSA,844 2,2

7、09,709 1,902,569 1,616,478 1,317,397 1,037,333 848,273 641,214 502,173 393,134 296,110 217,94 195,70 130,46 94,29 69,8 28,Incidence of AF Based on Presence or Absence of OSA,No OSA,Goals of Therapy,Relieve symptoms Prevent Stroke Prevent Heart Failure,Maintenance of SR,Pharmacologic,Stroke preventio

8、n,Nonpharmacologic,Class IA Class ICClass III -blocker,Catheter ablation Surgery (MAZE) Pacing,Pharmacologic Warfarin Thrombin inhibitor Heparin Aspirin Nonpharmacologic Removal / isolationLA appendage,Rate control,Pharmacologic Ca2+ blockers -blockers Digitalis Amiodarone Nonpharmacologic Ablate an

9、d pace,Prevent remodeling,ACE-I ARB,AF: TREATMENT OPTIONS,Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D.,Risk Factors for Thromboembolism in AF,High-Risk FactorsRecommended Therapy Previous CVA / TIA / EmbolismHigh-risk factor or 2 Mitral Stenosismoderate-risk factors Prosthetic heart valveC

10、oumadin INR 2-3 Moderate-Risk Factors(mechanical valve INR 2.5) Age 75 yrs HTN1 moderate-risk factor CHFASA or Coumadin DM EF 35%No risk factors Weaker-Risk FactorsASA 81-325mg daily Female CAD Thyrotoxicosis Age 65 74 yrs,AHA / ACC / ECS Guidelines 2006,D-Dimer Prediction of Risk,Evaluate whether e

11、levated D-dimer levels can predict thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy. Single-center, prospective, study of 269 pts with atrial fibrillation treated with warfarin D-dimer levels were measured End points were thromboembolic

12、events and combined cardiovascular events (thromboembolic events, cerebral hemorrhage, myocardial infarction, cardiovascular death). RESULTS: D-dimer levels were elevated ( or =0.5 microg/ml) in 63 (23%) patients. During an average follow-up period of 756 +/- 221 days: 10 (1.8%/year) thromboembolic

13、events (8 ischemic strokes, 1 transient ischemic attack, and 1 peripheral embolism 27 (4.8%/year) combined cardiovascular events (10 thromboembolisms, 9 deaths from heart failure, 3 sudden deaths, 2 myocardial infarctions, and 3 cerebral hemorrhages) Patients with elevated D-dimer levels experienced

14、 higher thromboembolic and combined cardiovascular events.,Sadanaga T, et. AL; J Am Coll Cardiol. 2010 May 18;55(20):2225-3.,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

15、 or 150 mg twice daily in a blinded fashion 2. Adjusted-dose warfarin in an unblinded fashion The median duration of the follow-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

16、received 110 mg of dabigatran (P0.001 for noninferiority) 1.11% per year in the group that received 150 mg of dabigatran ( P0.001 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 rece

17、iving 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 dabigatran (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

18、% per year with 150 mg of dabigatran (P=0.051). Conclusions Dabigatran 110 mg had rates of stroke and systemic embolism similar 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

19、RE-LY Steering Committee and Investigators NEJM Sept 17, 2009, No. 12, Vol 361: 1139-1151,AF THERAPY,ANTITHROMBOTIC RX,The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.,AFFIRM Trial: Rate vs Rhythm ControlManagement Strategy Trial,Design 5-year, randomized, parallel-group study comparing r

20、ate control vs. AARx attempt at NSR Primary endpoint: overall mortality Patient population 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:,202

21、7,2033,1925,1932,1825,1807,1328,1316,774,780,236,255,0,5,10,15,20,25,30,0,1,2,3,4,5,Mortality, %,Rate,Rhythm,p=0.078 unadjusted,Time (years),p=0.068 adjusted,The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.,* p=0.79,The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.,AFFIRM: Adver

22、se Events,100 80 60 40 20 0 ,Time (years),Percent With AF Recurrence,Rate Control,Raitt, et al. Am H J 2006,0,1,2,3,4,5,6,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, 494 (75),2, 4

23、84 (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 symptoms Con

24、tinuous 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 cardiomyopathy R

25、ate 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 patients with perma

26、nent 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, hospitalization

27、 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. (90% confi

28、dence 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 group; P0.001

29、 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.al, for the

30、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 the best of

31、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 Symptoms despit

32、e 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;63:193-197.

33、, 12 Months,100,80,60,40,20,0,Initial,One monthpost-CV,Six monthspost-CV,*P = 0.02,Patients in sinus rhythm (%),Length of timein AF prior tocardioversion,*,Class IA,Quinidine Procainamide Disopyramide,Class IC,Propafenone Propafenone SR Flecainide,Class III,Sotalol Amiodarone Dofetilide,Miller and Z

34、ipes. In: Braunwald, et al (eds). Heart Disease. 6th ed. 2001.,Procainamide, disopyramide, and amiodarone are not FDA-approved for treatment of AF.,Rhythm Control for AF: Commonly Used Oral Antiarrhythmic Drugs,AF Efficacy: Maintaining NSR 6 Months,ORGAN TOXICITY,Examples: Lupus, agranulocytosis, th

35、rombocytopenia, optic neuritis, pulmonary fibrosis, hepatitis, etc. Negligible: Dofetilide, flecainide, propafenone, sotalol, dronedarone Acceptable: Azimilide, disopyramide High: Amiodarone, procainamide, quinidine,Drug-Induced Proarrhythmia - Torsades,Factors Which InfluenceVentricular Proarrhythm

36、ia Risk,Hypokalemia, hypomagnesemia Long QT at baseline CHF / Decreased EF / Ventricular hypertrophy Bradycardia Female gender Reduced drug metabolism or clearance Amiodarone and Dronedarone has lowest risk (drondedarone cannot be started if baseline QTc/=500),AARx Choice,Heart diseaseAntiarrhythmic

37、 NoneIC or Dronedarone Vagal afibDisopyramide HTNIC (if no sig. LVH) then dronedarone CADSotalol CHF/SubstantialAmiodarone LVH,Prevention of atrial fibrillation by Renin-Angiotensin system inhibition,Schneider MP, et. Al. J Am Coll Cardiol. 2010 May 25;55(21):2299-307,Meta analysis of published clin

38、ical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation A total of 23 randomized controlled trials with 87,048 patients were analyzed. In primary prevention: 6 trials in hypertension, 2 trials in myocardial infarction, and 3 trials in hea

39、rt failure were included. In secondary prevention: 8 trials after cardioversion and 4 trials assessing the medical prevention of recurrence were included. Overall, RAS inhibition reduced the odds ratio for AF by 33% (p 0.00001), but there was substantial heterogeneity among trials. In primary preven

40、tion: RAS inhibition was effective in patients with heart failure and those with hypertension and left ventricular hypertrophy but not in post-myocardial infarction patients overall. In secondary prevention: RAS inhibition was often administered in addition to antiarrhythmic drugs, including amiodar

41、one, 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 inhibition is an emerging treatment for the primary and secondary prevention of AF,Alternatives to Drug therapy“Non-Pharmacologic Therapy”,Coumadin LAA cl

42、osure (Watchman) Rate Control AVN RFA + PCMK AARx Adjunctive AFL RFA AARX Curative Afib RFA,WATCHMAN LAA Filter System,Complete AVN ablation,Pacemaker Placement,AVN RF ablation,Objective Benefits of AV nodal Ablation,Rodriguez LM. Am J Cardiol. 1993;72:1137-1141.,A Left ventricular ejection fraction

43、 (%),B Left ventricular end systolic diameter (mm),70,60,50,40,30,20,Before,After,LVEF (%),mean 54 + 7,p 0.001,mean 43 + 8,55,50,45,35,30,20,Before,After,LVESD (mm),mean 34 + 5,p 0.003,mean 40 + 5,40,25,Complete AVN Ablation,Advantages: 100% efficacy 85% symptomatic improvement Improved EF (LV remod

44、eling) Eliminates need for rate control drugs Disadvantages: Pacemaker dependant Good Candidates: Tachy / Brady Syndrome PCMK in Place CHF with BiV device Medication refractory / intolerant Elderly,60 F with PAF treated with RythmolPresented with recurrent tachycardia,Atrial Flutter Circuit,Atrial F

45、lutter Circuit,Atrial Flutter Ablation,Atrial Flutter RFA,Atrial Flutter Ablation,Approximately 15% of AF patients treated with an AA will develop AFL Advantages: 95% efficacy 80% arrhythmia control if AARx continued As primary Rx: RFA more effective than AARx Disadvantages: Invasive Good Candidates

46、: Typical AFL (IVC / TV isthmus) Primary AFL or AARx related AFL,Focal Origin of Atrial FibrillationHassaiguerre M, NEJM, 1998,94% of AF triggers from Pulmonary Veins “90 95% of all AF is initiated by PV ectopy”,RA,LA,CS,FO,SVC,IVC,Pulmonary Veins,17,31,6,11,74 yo medically refractory AF, Echo Normal AA Rx - Verapamil, Rythmol, Betapace, Norpace,Lasso Catheter,Circular Mapping & Ablation Catheter i