Management of Atrial Fibrillation in 2010 John D. Hummel, MD Ohio State University Medical Center Ross Heart Hospital Columbus, Ohio Learning Objectives • Understand the risk factors for atrial fibrillation. • Understand the guidelines for anticoagulation and where there is latitude for physician decision making. • Be able to determine when patients should be evaluated for curative ablation. Projected Number of Adults With AF in the US: 1995 to 2050. Adults with AF, MM 6 5 4.78 5.16 5.42 5.61 4.34 4 3.80 3 2 2.08 2.26 2.44 2.66 2.94 3.33 1 Year Go A, et al. JAMA. 2001;285:2370-2375. 20 60 20 50 20 45 20 40 20 35 20 30 20 25 20 20 20 15 20 10 20 05 20 00 19 95 0 Atrial Fibrillation: Costs to the Health Care System ALOT!! 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 strokes Estimated US cost burden 15.7 billion Classification of Atrial Fibrillation ACC/AHA/ESC Guidelines First Detected Paroxysmal (Self-terminating) Persistent (Not self-terminating) Permanent DIAGNOSTIC WORKUP Identify Causes and Risk Factors • • • • • • • • • • Minimum Evaluation History and physical – BP, CV dz Electrocardiogram – 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 Incidence of AF Based on Presence or Absence of OSA 20 – 15 – OSA Cumulative 10 – Frequency of AF (%) 5– No OSA 0– 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years Number at Risk OSA No OSA 844 709 569 478 397 333 273 214 173 134 110 94 70 46 29 8 2,209 1,902 1,616 1,317 1,037 848 641 502 393 296 217 195 130 94 69 28 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 Gami, et al. JACC 2007;49:565-71 Goals of Therapy 1. Relieve symptoms 2. Prevent Stroke 3. Prevent Heart Failure AF: TREATMENT OPTIONS Rate control Pharmacologic • Ca2+ blockers • -blockers • Digitalis • Amiodarone Nonpharmacologic • Ablate and pace Prevent remodeling Maintenance of SR Pharmacologic Class IA Class IC Class III -blocker ACE-I ARB Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D. Stroke prevention Nonpharmacologic Pharmacologic • Warfarin • Thrombin inhibitor • Heparin • Aspirin Catheter ablation Surgery (MAZE) Nonpharmacologic Pacing • Removal / isolation LA appendage Risk Factors for Thromboembolism in AF High-Risk Factors Previous CVA / TIA / Embolism Mitral Stenosis Prosthetic heart valve Moderate-Risk Factors Age > 75 yrs HTN CHF DM EF < 35% Weaker-Risk Factors Female CAD Thyrotoxicosis Age 65 – 74 yrs AHA / ACC / ECS Guidelines 2006 Recommended Therapy High-risk factor or > 2 moderate-risk factors Coumadin INR 2-3 (mechanical valve INR > 2.5) 1 moderate-risk factor ASA or Coumadin No risk factors ASA 81-325mg daily D-Dimer Prediction of Risk Evaluate whether elevated 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 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: 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 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 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 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 received 110 mg of dabigatran (P<0.001 for noninferiority) 1.11% per year in the group that received 150 mg of dabigatran ( P<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 dabigatran (P<0.001) 0.10% per year with 150 mg of dabigatran (P<0.001). 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 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 RE-LY Steering Committee and Investigators NEJM Sept 17, 2009, No. 12, Vol 361: 1139-1151 AF THERAPY ANTITHROMBOTIC RX AND RHYTHM CONTROL OR ? RATE CONTROL 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 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% The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. AFFIRM: All-Cause Mortality 30 Rate Rhythm 25 Mortality, % 20 p=0.078 unadjusted 15 p=0.068 adjusted 10 5 0 0 1 2 3 Rhythm N: 2033 1932 Time (years) 1807 1316 Rate N: 2027 1925 1825 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. 1328 4 5 780 255 774 236 AFFIRM: Adverse Events Rate Rhythm Ischemic stroke 77 (5.5%)* 80 (7.1%)* INR < 2.0 27 (35%) 17 (21%) Not taking warfarin 25 (32%) 44 (55%) * p=0.79 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. Time to first recurrence of AF. Time 0 is the day of randomization 100 – Rate Control 80 – Rhythm Control Percent With AF Recurrence 60 – 40 – Log rank statistic = 58.62 p < 0.0001 20 – 0– 0 1 2 3 4 5 6 Time (years) N, Events (%) Rate control: 563, 3 (0) 167, 383 (69) 98, 440 (80) 42, 472 (87) 10, 481 (92) 2, 484 (95) Rhythm control: 729, 2 (0) 344, 356 (50) 250, 422 (60) 143, 470 (69) 73, 494 (75) 18, 503 (79) Raitt, et al. Am H J 2006 Implications • AFFIRM has demonstrated that rate control is an acceptable primary therapy in a selected high-risk subgroup of AF patients with minimal symptoms • Continuous anticoagulation seems warranted in all patients with risk factors for stroke – Asymptomatic recurrences 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 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, hospitalization 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% confidence interval, –7.6 to 3.5; P<0.001 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; P<0.001 with fewer total visits (75 vs. 684]; P<0.001). 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 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 circumstances pacing support is sometimes required Goal: Chronic afib – mean 24hr HR < 80-90 bpm (?) APPROACHES TO AF THERAPY Rate control plus anticoagulation preferred • • • • • • No or lesser AF symptoms Longer AF Hx More SHD Toxicity Risk Elderly Greater risk of proarrhythmia Rhythm control preferred • • • • • Greater AF symptoms Symptoms despite rate control Younger age No or lesser SHD Rx option of class IC AAD In anticoagulation candidates, continue anticoagulation indefinitely Atrial Fibrillation Length of time in AF prior to cardioversion • Duration of AF is the best predictor of recurrent AF after cardioversion Patients in sinus rhythm (%) 100 < 3 Months 3 - 12 Months > 12 Months 80 60 40 * 20 0 *P = <0.02 Initial Dittrich HC. Am J Cardiol. 1989;63:193-197. One month post-CV Six months post-CV Rhythm Control for AF: Commonly Used Oral Antiarrhythmic Drugs Class IA Class IC Class III Quinidine Propafenone Sotalol Procainamide Propafenone SR Amiodarone Disopyramide Flecainide Dofetilide Procainamide, disopyramide, and amiodarone are not FDA-approved for treatment of AF. Miller and Zipes. In: Braunwald, et al (eds). Heart Disease. 6th ed. 2001. AF Efficacy: Maintaining NSR > 6 Months 70 60 NSR, % 50 40 30 20 10 0 No drug Quin Diso Prop Flec Sot Dof Azim Amio ORGAN TOXICITY • Examples: – Lupus, agranulocytosis, thrombocytopenia, 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 Influence Ventricular Proarrhythmia 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 disease Antiarrhythmic None Vagal afib HTN IC or Dronedarone Disopyramide IC (if no sig. LVH) then dronedarone Sotalol Amiodarone CAD CHF/Substantial LVH Prevention of atrial fibrillation by ReninAngiotensin system inhibition 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 controlled 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 included. 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-myocardial 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 inhibition is an emerging treatment for the primary and secondary prevention of AF Schneider MP, et. Al. J Am Coll Cardiol. 2010 May 25;55(21):2299-307 Alternatives to Drug therapy “Non-Pharmacologic Therapy” Coumadin – LAA closure (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 70 55 50 mean 54 + 7 60 mean 34 + 5 LVESD (mm) LVEF (%) 45 50 mean 43 + 8 40 p < 0.001 30 40 mean 40 + 5 35 30 p < 0.003 25 20 20 Before After A Left ventricular ejection fraction (%) Rodriguez LM. Am J Cardiol. 1993;72:1137-1141. Before After B Left ventricular end systolic diameter (mm) Complete AVN Ablation Advantages: 100% efficacy 85% symptomatic improvement Improved EF (LV remodeling) 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 Rythmol Presented with recurrent tachycardia Atrial Flutter Circuit Atrial Flutter 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: Typical AFL (IVC / TV isthmus) Primary AFL or AARx related AFL Focal Origin of Atrial Fibrillation Hassaiguerre M, NEJM, 1998 • 94% of AF triggers from Pulmonary Veins • “90 – 95% of all AF is initiated by PV ectopy” RA LA SVC 17 31 FO Pulmonary Veins 6 IVC CS 11 74 yo medically refractory AF, Echo – Normal AA Rx - Verapamil, Rythmol, Betapace, Norpace I II III V1 RSPV dist RSPV prox LIPV RA * Lasso Catheter Circular Mapping & Ablation Catheter in Right Superior Pulmonary Vein Atrial Fibrillation Ablation Atrial Shell and Cardiac MRI 45 yo F with medically refractory Highly Symptomatic PAF 45 yo F with Medically Refractory PAF CT Scan / Carto Images – PA View 45 yo with PAF Conversion of AF to NSR, LSPV with AF Abl Lasso LSPV CS Current State of Curative Catheter-Based RFA Procedural Success & Complications • Total Patients > 1300 (65% PAF) • Expected success @ 1yr – ≈ 70% after first procedure – ≈ 80% after second procedure • Complications ≈ 1 to 3% – – – – – Tamponade – 0.6% Pulmonary vein stenosis – 0.6% TIA / CVA – 0.5% Esophageal-LA fistula - 0 Groin Bleeding / Hematoma (Last 200 pts complications < 1%) Atrial Fibrillation: Ablation vs Drug Rx. Ablation 80% success PV stenosis AE fistula TIA/CVA Drug Rx. 50% success Proarrhythmia End Organ Toxicity No Free Lunch Torsades AE fistula PV stenosis Current State of Curative Catheter-Based RFA Who is a good candidate? Symptomatic / Frequent AF Limited Heart Dz EF > 35% LA < 5.5cm No MS / Rheumatic Dz Younger Patients No LA thrombus or Hx of CVA Medically Refractory / Intolerant (Ablation now second line therapy) Atrial Fibrillation New Technology Coming Your Patients Way at Ohio State University Stereotaxis – Magnetic Catheter Navigation Ablation Frontiers Cryoablation Balloon Endosense A-Fib vs. EP Labs AF TREATMENT GOALS • AF is rarely life-threatening and is typically recurrent • Treatment goals in symptomatic pts – frequency of recurrences – duration of recurrences – severity of recurrences • Minimize risk of tachycardia induced cardiomyopathy • Safety is primary concern