Atrial Fibrillation Wat ur di-n 2 no Ned Gutman 6 August, 2009
2 goals in treating AF Alleviation of symptoms Reduce risk of stroke
Anticoagulation CHADS score Future anticoagulants Rate vs Rhythm control New therapies Drugs Ablation
Anticoagulation: CHADS score CHF 1 point Hypertension 1 Age >75 1 Diabetes 1 H/O TIA or stroke 2 0 points: Aspirin 1-2 points: aspirin vs warfarin 3+ points: warfarin
Anticoagulation: CHADS risk Events per 100 person-years Score Warfarin No Warfarin 0 0.25 0.49 1 0.72 1.52 2 1.27 2.50 3 2.2 5.27 4 2.35 6.02 5 or 6 4.6 6.88 Go, AS Hylek, EM, Chang, Y JAMA 2003;
Warfarin risk/benefit balance 20 15 Odds ratio 10 5 1 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 International normalized ratio Ischemic stroke Intracranial bleeding Fuster V et al. Circulation. 2006;114:e257-e354.
What % of patients have INR within therapeutic range? A 95% B 85% C 75% D 65% F 55%
Adequacy of anticoagulation of anticoag Even with intentions to follow the guidelines, and with patient cooperation, effective anticoagulation is erratic at best INR often deviates outside of the therapeutic range Dietary fluctuations Changes in bowel flora Interactions Formulation substitution Lab errors Other Time that INR is in therapeutic range is variable even when patients are managed carefully Courtesy of JA Reiffel, MD.
Patients don t like Warfarin Rat poison Frequent blood test Bruising Food interactions Inconvenient to travel
Home INR monitor Fingerstick, just like glucometer Immediate results Flexibilty for travel/shut-ins Current usage mandates weekly testing Requires insurance approval
Rivaroxaban Factor Xa inhibitor Once daily oral dosing Effective 3 hours after 1st dose No food interactions Favorable results in preventing post-op DVT after hip & knee surgery Increased major bleeding (0.4 vs 0.2%) Rare liver events with 1 death No monitoring of coagulation parameters
Rivaroxaban: ROCKET AF Patients with AF Double blind, Warfarin vs Rivaroxaban CHADS score 3 15,000 patients enrolled
Rate vs Rhythm control No survival benefit with rhythm control Stroke risk not different Rhythm control does not obviate need for anticoagulation Symptoms often related to optimizing rate All antiarrhythmics have risks
misconceptions Misconceptions about rhythm-control strategy N = 148 PCPs from 36 US states 80 73 64 60 55 Respondents (%) 40 20 0 Helps avoid long-term anticoagulation Decreases mortality Decreases stroke McCabe JM et al. Am J Cardiol. 2009;103:535-9.
Cumulative mortality (%) Affirm outcome AFFIRM: Primary outcome N = 4060 with AF Age 65 years or 1 risk factor for stroke or death 1 st AF episode: 36% No contraindications for warfarin Follow-up 3.5 years Predominant diagnosis Hypertension 51%, CAD 26% n = 2033 rhythm control n = 2027 rate control 30 25 20 15 10 5 0 P = 0.08 Rhythm control Rate control 0 1 2 3 4 5 Time (years) AFFIRM Investigators. N Engl J Med. 2002;347:1825-33.
Rate control Typically achieved with 1-2 meds Usual agents: B-blockers Ca-blockers (diltiazem, verapamil) Digoxin- often avoid in very elderly due to risk of toxicity Amiodarone used rarely only when unable to tolerate other agents
Rhythm control Success is not the same as cure or 100% reduction in AF burden Amiodarone most effective but also has most side effects Avoid Class I agents in patients with CAD or CHF Avoid Sotolol in patients with LVH
Rhythm control Very hi recurrence rate of AF Many AF episodes will be asymptomatic Under-recognize true AF burden Need to maintain anticoag in all patients, unless low CHADS score
Amiodarone Requires monitoring of LFTs & TFTs Annual PFTs - measure diffusing capacity Effects digoxin and warfarin levels, usually reduce both to 1/2 dose Corneal micro deposits up to 90% Frequent GI side effects (30%) Less pro-arrhythmia (TdP) than other agents Co- administration with ACEI/ARB even more effective
AF prevention with ACEI or ARB plus antiarrhythmic AF pevention drug w ACEI + Amio N = 177 with lone paroxysmal AF 1.0 0.9 0.8 Group 2 Amiodarone + losartan 0.7 Group 3 Amiodarone + perindopril AF recurrencefree survival 0.6 0.5 0.4 Group 1 Amiodarone 0.3 0.2 0.1 0.0 Group 1 vs 2: P = 0.006 Group 1 vs 3: P = 0.04 Group 2 vs 3: P = 0.47 0 90 180 270 360 450 540 630 720 810 Time after randomization (days) Yin Y et al. Eur Heart J. 2006;27:1841-6.
Dronedarone new amiodarone Does not have I moiety Less side effects, especially thyroid and pulmonary Better than placebo in reducing AF, but no good head-head trials May increase death in CHF patients
ACC guidelines 4 rhythm control ACC/AHA/ESC 2006 AF rhythm-control guidelines Maintenance of SR No (or minimal) heart disease Hypertension CAD HF Flecainide Propafenone Sotalol Substantial LVH No Yes Dofetilide Sotalol Amiodarone Dofetilide Amiodarone Dofetilide Catheter ablation Amiodarone Catheter ablation Amiodarone Dofetilide Flecainide Propafenone Sotalol Catheter ablation Amiodarone Catheter ablation Catheter ablation Fuster V et al. Circulation. 2006;114:e257-e354.
Pulmonary vein ablation In symptomatic patients requiring rhythm control, if at least 1 antiarrhymic has been ineffective or not tolerated->rfa AF is often triggered by ectopic beats/foci originating from PV Isolating PV by RFA prevents many of these triggers from entering the atria TEE to exclude appendage clots, transseptal puncture
Pulmonary vein ablation More effective than drugs in reducing AFib Even after success, should continue anticoagulation 30% require more than 1 procedure Most effective for paroxysmal rather than chronic AF
Catheter ablation vs antiarrhythmic drug therapy for AF Cath ablation vs adt N = 432 with AF; Meta-analysis of 4 randomized clinical trials Source ADT more effective CPVA more effective Risk ratio (95% CI) % Weight Pappone et al, 2006 3.86 (2.65-5.63) 37.5 Stabile et al, 2006 6.43 (2.91-14.21) 18.1 Wazni et al, 2005 4.22 (2.14-8.32) 22.0 Krittayaphong et al, 2003 2.00 (1.02-3.91) 22.4 Overall (95% CI) 3.73 (2.47-5.63) 0.04 0.20 1.00 5.00 25.00 Risk ratio ADT = antiarrhythmic drug therapy CPVA = circumferential pulmonary vein ablation Noheria A et al. Arch Intern Med. 2008;168:581-6.
A4 study: Catheter ablation vs antiarrhythmic drug therapy for AF A4 cath abl vs adt N = 112 with paroxysmal AF resistant to 1 AAD 100.0 80.0 Freedom 60.0 from recurrent AF (%) 40.0 20.0 0.0 0 Logrank P < 0.0001 RF 50 100 150 200 250 300 350 400 Follow-up (days) ADT RF = radiofrequency catheter ablation Jaïs P et al. Circulation. 2008;118:2498-505.
Worldwide survey of catheter ablation World survey of RFA N = 8745 with AF treated at 90 centers 12,830 procedures, with 27% of patients undergoing >1 procedure 6% major complication rate 4 deaths (0.05%) 107 tamponade (1.22%) 20 strokes (0.28%) 47 TIA (0.66%) 94 PV stenosis (1.3%) Cappato R et al. Circulation. 2005;111:1100-5.
US US experience with catheter RFA ablation N = 517 with AF undergoing catheter ablation treated at 1 US institution 641 procedures 32 major complications (5%) 7 CVA (1.1%) 8 cardiac tamponade (1.2%) 1 PV occlusion (0.16%) 11 vascular injury (1.7%) No deaths or esophageal injury Complication rate 9% 1 st 100 patients, 4% thereafter Predictors of complications Female gender Age >70 years Spragg DD et al. J Cardiovasc Electrophysiol. 2008;19:627-31.
Complications of RFA Formation of atrio-esophageal fistula Rare Often fatal Occurs with more extensive LA ablations
Complications of RFA Pyloric spasm & gastric hypomotility Occurred 4/367 patients Injury to vagus nerve surrounding esophagus Post ablation indigestion is common? if related to transient nerve dysfunction
Atrial Fibrillation Recurrence AF recurs in 35% within 2 weeks (early) May be transient, related to pericarditis Short term use of anti-arrhythmics for 2-3 months 25% may undergo more than 1 ablation Atrial Flutter may occur due to new reentrant circuits created by RFA scar
HRS/EHRA/ECAS Expert Consensus Statement: Indications Consensus for catheter statement ablation of AF Indications Symptomatic AF refractory or intolerant to 1 Class 1 or 3 antiarrhythmic drug Selected symptomatic patients with HF and/or EF Should not be considered as 1 st line therapy, except in rare clinical situations Repeat procedures should be delayed for 3 months, if symptoms can be controlled with medical therapy Calkins H et al. Heart Rhythm. 2007;4:816-61.
Possible upstream treatments and mechanisms Upstream for treatments AF prevention ACEIs/ARBs Statins Glucocorticoids Omega-3 fatty acids Physical activity Inflammation Oxidative stress RAAS activity Endothelial function Autonomic nervous system activity Vascular stability Atrial remodeling Stabilize left atrial endocardium Atrial fibrillation Courtesy of CJ Pepine, MD.
AF prevention w RAAS Trials of RAAS inhibition in AF prevention Favors treatment Favors control ACEIs CAPP GISSI HOPE SOLVD STOP-H2 TRACE Ueng Van den Berg Subtotal ARBs CHARM LIFE Madrid ValHeFT Subtotal Total Captopril Lisinopril Ramipril Enalapril Enalapril Trandolapril Enalapril Lisinopril Candesartan Losartan Irbesartan Valsartan Subtotal Total 0.1 0.2 0.5 1.0 2.0 5.0 RR* (95% CI) *Random-effects model Salehian O et al. Am Heart J. 2007;154:448-53. Healey JS et al. J Am Coll Cardiol. 2005;45:1832-9.
Statins in prevention of AF (1 st episode or AF recurrence) Statins Study Statin Control or subcategory n/n n/m Favors treatment Favors control MIRACL 93/1539 96/1548 Tveit 18/51 17/51 Dernellis 14/40 36/40 ARMYDA 3 35/101 56/99 Chello 2/20 5/20 Ozaydin 3/24 11/24 Total (95% CI) 1775 1782 Total events: 165 (Statin), 221 (Control) Test for heterogeneity: Chi 2 = 29.47, df = 5 (P < 0.0001), I 2 = 83.0% Test for overall effect: Z = 2.35 (P = 0.02) Not assessed in this meta-analysis: Degree of LDL-C Statin dose 0.1 0.2 0.5 1 2 5 10 OR (random) 95% CI Fauchier L et al. J Am Coll Cardiol. 2008;51:828-35.
Role of pacemakers Back up pacemakers are indicated for symptomatic brady arrhythmias Asymptomatic patients, while awake pause >3.0 sec escape rate <40
Pacemakers to prevent A Fib Controversial evidence-class III Not indicated unless pacemaker appropriate for other reasons Pace above baseline rate, reducing atrial refractoriness and prevent sinus pauses Recognize A Fib episodes, algorithm to provide rapid/burst atrial pacing, may convert back to sinus
4 things to remember Most patients with Afib should be considered for long term anticoagulation Rate control strategy is at least as good as rhythm control in reducing CV events Amiodarone is the most efficacious agent in reducing AF burden but has most potential side effects Ablation offers improved AF control in select patients