A 35 yo female presents increasing fatigue and shortness of breath for several days. She is found to be in atrial fibrillation.

Transcription

1 Ryan G. Aleong Cardiology Department University of Colorado A 35 yo female presents increasing fatigue and shortness of breath for several days. She is found to be in atrial fibrillation. 1. Initiation of IV heparin 2. Warfarin to maintain an INR between 2.0 to 3.0 for 4 weeks post cardioversion 3. Given young age, no echocardiogram prior to cardioversion necessary 4. Electricity

2 1. Dronedarone 2. Amiodarone 3. Dofetilide 4. Catheter Ablation 1. aspirin 2. warfarin 3. Discussion with the patient regarding aspirin vs. warfarin 4. Clopidogrel Epidemiology Presentation Diagnostics Management Options Reducing Thrombo Embolic complications Rate Control Rhythm Control

3 Prevalence 0.4% to 1% of general population Increasing prevalence with age 8% of patients older than 80 y.o. Median age ~75 y.o. Conditions Associated with AF: HTN, CHF, Ischemic HD, Valvular HD, Diabetes Less common among African Americans AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study, JAMA, 2001

4 RR compared To NSR In the SOLVD Prevention and Treatment Trials, Atrial Fibrillation was an Independent Predictor of All Cause Mortality and Pump Failure Death, Retrospective Analysis Dries, DL, JACC, 1998 Study NYHA Class % AF EF: Sinus vs. AF Multivariate Predictor of Mortality? V HeFT I (1993) NYHA II IV 16% 30% vs. 31% No V HeFT II NYHA II IV 13% 29% vs. 32% No SOLVD (1998) NYHA I IV 6% 27% vs. 26% Yes VA ICD Cohort NYHA II IV 27% vs. 26% Yes

5 EKG: Sinus P waves replaced by rapid fibrillatory waves that vary in amplitude, shape and timing Primary (Lone) AF: General young patients (< 60 yo) without clinical or echo evidence of cardiopulmonary disease Secondary AF: Occurs in the context of MI, cardiac surgery, pericarditis, myocarditis, hyperthyroidism, pulmonary embolism, pneumonia, other acute pulmonary disease, toxins (alcohol, caffeine) other arrhythmias (atrial flutter, WPW, AVNRT) Treat underlying condition Obesity: Independent risk factor to AF Decreased BMI associated with decreased LA size Heart Disease Valvular heart disease, especially MV disease LVH Associated: HTN, CAD, amyloid Cardiomyopathies: HCM, restrictive CM Congenital heart disease, ASD Sleep Apnea

6 Cardioversion has failed or not been attempted Pathophysiology of Paroxysmal Atrial Fibrillation: PAC s from the pulmonary veins Haïssaguerre M et al. N Engl J Med 1998;339: DE MRI Identifies areas of fibrosis as observed in green J Cardiovasc Electrophysiol Aug 30

7 Atrial Stretch: Promotes Atrial Fibrosis Changes in Atrial Substrate due to initial AF Connexin expression changes Calcium channel downregulation Shortening of atrial action potential Renin angiotensin aldosterone system Inflammatory Changes Genetics: Familial patterns more apparent, several K channel mutations described Palpitations, chest pain, SOB Symptoms severity may decrease as AF pattern changes from paroxsymal to permanent Tachycardia induced cardiomyopathy Syncope (uncommon): Conversion pauses, rapid ventricular rates, association with cardiac disease (AS, HCM) Minimum Evaluation History: Characterization of symptoms EKG: Rhythm, pre excitation, LVH, prior MI Echo: Valvular disease, LV size and function, LA/RA size, LA thrombus, pericardial disease Holter or Event monitor if AF undocumented Blood tests: Thyroid, Cr, LFT s Additional Tests EP Study: Detect triggering arrhythmias (AVNRT, AVRT, Atrial Flutter); Lone AF

8 Thrombus most often forms in left atrial appendage Generally accepted that requires 48 hrs to form Not well seen with transthoracic echo Stunning of LAA increases risk of thrmobus formation after CV Regional increased coagulation system in LA Interplay between increased stasis, endothelial dysfunction and comorbid factors Risk Factors Age < 75 yo HTN Systolic Dysfunction Diabetes Mellitus Previous TIA/CVA Rate Control Prevention of Thromboembolism Rhythm control Initial strategy may not work and alternate strategies may be pursued

9 N = 171, 393 patients Hatched area represents warfarin use as documented in first 30 days after AF diagnosis Zimetbaum, American Journal of Medicine, 2010 Aspirin Aspirin or Warfarin Warfarin

10 Trial Comparison Mechanism of camparin drug ACTIVE W Trial 1 SPORTIF Trials 2 AMADEUS 3 ASA + Clopidogrel vs. warfarin Ximelagratan vs. warfarin Anti platelet Direct thrombin inhibitor Idraparinux vs. warfarin Injectable factor X inhibitor Favors Warfarin Warfarin warfarin RE LY 4 Dabigatran vs. warfarin Direct Throbin Inhibitor Noninferior, may favor dabigatran Note that these are non inferiority trials, require large sample sizes, expensive; Generalizability of results difficult 1. Lancet, 2006; 367: Lancet, 2003; 362: 1691; Note Ximelagratan withdrawn due to liver issues 3. Lancet, 2008; 371: 315; Note Idraparinux with excess bleeding 4. NEJM, 2009; 361: 1139 Watchman Device: Non inferior to Warfarin in PROTECT AF trial Amplatzer Cardiac Plug device Ongoing Trial

11 ACE inhibitors and ABB s may decrease indience of AF Decrease atrial pressure/ fibrosis HMG CoA Reductase Inhibitors (Statins): Decrease AF recurrences,? Antiinflammatory AFFIRM (Atrial Fibrillation Follow up Investigation of Rhythm Management) Mean Age 69 yo No difference in mortality or stroke rate Similar development/deterioration of HF Trend towards increased mortality in rhythm control arm (26.7%vs. 25.9%, p 0.08) Inconsistent results regarding QOL improvement in each strategy Sinus rhythm and warfarin use associated with improved survival Problems with AFFIRM: Did not study young patients with normal hearts or those with symptomatic AF Rate control or rhythm control strategy should not affect anticoagulation requirement Symptoms should dictate rate vs. rhythm control strategy

12 Reasons to Pursue Improve hemodynamics Avoid Tachycardia Mediated Cardiomyopathy May improve symptoms ACC/AHA Guidelines Assess rates at rest and during exercise Beta blockers/ccb reasonable in acute setting (in absence of pre excitation) Digoxin or Amiodarone reasonable in AF/CHF AV Node Ablation reasonable in unable to control HR with medications AFFIRM: beta blockers more effective than CCB in achieving adequate rate control Calcium Channel Blockers: Avoid in heart failure due to negative inotropic effects Digoxin: Modest rate control at rest, best seen in heart failure Pacing Improves safety of AVN agents May decrease rates due to retrograde AVN penetration Rate regularization may improve symptoms HR 0.84 (90% CI, 0.58 to 1.21) Van Gelder IC et al. N Engl J Med 2010;362:

13 Patients with symptoms or tachycardia mediated cardiomyopathy due to rapid rates not well controlled with medications Meta analysis of 21 trials (n= 1181) showed AVN ablation improved symptoms, QOL and healthcare utilization Ablate and Pace Trial: Patients with reduced systolic function at baseline improved (Kay, JICE, 1998) Cons: Small risk of SCD, pacemaker dependent, RV pacing Staged approach Anticoagulation rules apply with either pharmacologic or electrical CV Pharmacologic CV Less efficacious than electricity Most effective when within 7 days of initiation of AF Pill in the Pocket with flecainide or propafenone reasonable in structurally normal hearts after tested in hospital Dofetilide, Ibutilide and Amiodarone have proven efficacy Vernakalant: Investigational

14 Flecainide: Multiple trials show effectiveness Propafenone: UK PSVT reduced AF 51% vs 27% Sotalol Effectiveness as Propafenone (maybe) Reverse Use Dependence TdP SAFIRE D Trial: Dofetilide 58% vs. 25% DIAMOND: Dofetilide 79% vs 42% TdP: 0.8% Amiodarone: Most Effective at maintaining sinus rhythm; Effective for Rate Control

15 High Rate of discontinuation due to toxicity (up to 18%) Photosensitivity, pulmonary toxicity, polyneuropathy, GI upset, bradycardia, torsades de pointes(rare), hepatic toxicity, thyroid dysfunction, eye complications QT prolonging medications may Have a higher risk of TdP due to Dispersion of repolarization Dronedarone Mildly Better than Placebo in Preventing AF Recurrence ANDROMEDA: Recently Decompensated Heart Failure (NYHA II IV) terminated Due to Excess mortality in dronedarone Arm; Avoid EF < 35% or NYHA > I

16 Copyright restrictions may apply. Catheter Ablation Superior to Anti-Arrhythmic Treatment for Paroxsymal Atrial Fibrillation Patients Wilber, D. J. et al. JAMA 2010;303: Catheter ablation is a reasonable alternative to pharmacological therapy to prevent recurrent AF in symptomatic patients with little or no LA enlargement. (Level of Evidence: C) Expanding use of catheter ablation in patients with persistent and permanent atrial fibrillation

17 More patients receiving ablation Sicker Patients receiving ablations Higher Success Rates No change overall complications, but More atypical atrial flutters Atrial Fibrillation Represents a Growing issue Assessing Thrombo Embolic Risk is of paramount importance Catheter Ablation may improve rhythm control compared to medications, however further studies required