Atrial Fibrillation

1. Atrial Fibrillation BGSMC Cardiology Study Group January 6, 2011 Mohamad Lazkani, MD Tomas Rivera-Bonilla, MD Nick Sparacino, DO

2. Introduction • History William Harvey *1628 Robert Adams reported *1827 Etienne Marey *1863 Sir Thomas Lewis *1909 Bootsma and coworkers *1970 William Kannell and colleagues *1982

3. Epidemiology Most common dysrrhythmia Overall lifetime risk ~25% 416,000 hospital discharges in 2001 Avg medicare cost of hospitalization 6k, not including followup, procedures (echo, etc), meds 50-90% increase in mortality from Framingham study

4. Recognizing A Fib • Classic irregularly irregular pulse • Remember to take pulse at carotids, not peripherally • EKG WITHOUT P WAVES • Note all that is irregular is not a fib…

5. Classification of Atrial Fibrillation • Presence of other cardiac disease • Lone atrial fibrillation • Valvular atrial fibrillation • Type of presentation • “First detected episode” • Recurrent • “Persistence” • Paroxysmal – self converts within 7 days • Persistent – requires pharmacologic or electrical cardioversion, but does convert • Permanent – refractory to attempts

6. Causes • Valvular disease • MS is classic, but any state that can cause dilation of the atria… aka any valvular issue • Hypertension – Most common in US • Alcohol – “holiday heart” • MI • Familial • Mutation in slow K channel causes increased inward K flux and decreased refractory period • Hyperthyroid • Hypersympathetic states • Post-operative

7. Pathophysiology - Initiation Pulmonary vein muscle sleeves 1)Increased automaticity 2)Epicardially contiguous with myocardium of atria 3)Less commonly in the similarly arranged muscular sleeves of the proximal SVC

8. Pathophysiology - Perpetuation 2 Preconditions for reentry Heterogeneous conduction Allows preferential unidirectional conduction Allows impulse to still be traveling down slow path while fast path is repolarizing Short refractory period Allows fast path to be “primed” for depolarization by the time the slow pathway reaches previously depolarized “fast” tissue

9. Mechanism of Conduction The AV node limits conduction during AF. There appear to be 2 distinct atrial inputs to the AV node, posteriorly via the crista terminalis and anteriorly via the interatrial septum.

10. Remodeling – “A fib begets A fib” 2 Mechanisms Decrease in fast Na channel and L-type Ca channel expression = Short Refractory Period Increased metabolic and mechanical stress leads to reparative and reactive fibrosis = Heterogenous Conduction Hmm… Short refractory period and heterogeneous conduction, that sounds familiar…

11. Consequences… Decrease in Cardiac Output Thromboembolism Tachycardic Cardiomyopathy

12. Why treat Atrial Fibrillation? • Loss of synchronous atrial mechanical activity • Irregularity of ventricular response • Inappropriately rapid heart rate • One of every 6 strokes occurs in patients with AF. The overall risk of thromboembolism is approximately 5% per year • In the Framingham cohort, (OR) for total mortality was 1.5 for men and 1.9 for women with AF after the analysis was adjusted for age, overt heart disease, and other risk factors • Rheumatic heart disease and AF had a 17-fold increased risk of stroke. The AR* on rheumatic heart disease was 5 times greater than in those with nonrheumatic AF

13. Management of Atrial Fibrillation • The dilemma as to whether to try rhythm control, or to accept the arrhythmia and control the ventricular rate Rate control strategies : symptomatic improvement is achieved solely because of better control of the ventricular rate Rhythm control strategies: It has been demonstrated that restoration of sinus rhythm is associated with improvements in exercise capacity and peak oxygen consumption, both in patients with structural heart disease and in those with normal hearts. However, drugs used for rhythm control may cause serious proarrhythmia.

14. Dilemma of Rate vs Rhythm

15. Pharmacological Agents for Rate and Rhythm Control

16. Nonpharmacological Approach for AFIB • Surgical Ablation • Catheter Ablation • Suppression of AF by Pacing • Internal Atrial Cardioverter/ Defibrillators • The Radiofrequency Ablation for Atrial Fibrillation Trial (RAAFT), will better assess the late recurrence rates of AF.The effect of ablation on mortality rates, quality of life, and health care costs will probably be better established during the coming years. • The CABANA (Ablation vs Drug Therapy for Atrial Fibrillation) pilot study, will be followed by a 3000-patient CABANA mortality trial, in which 1500 patients older than 65 years or younger than 65 years but with other risk factors for stroke will be randomly assigned to drug therapy, and an additional 1500 such patients will be randomly assigned to ablative intervention.

17. Anticoagulation Therapy • CHADS score • Gender (female sex) • Mitral Stenosis • Dilemma: ACC/AHA/ESC AF Guidelines. • Six randomized trials have compared adjusted-dose warfarin to placebo reduction in stroke averaged about 60% • Six randomized trials comparing aspirin to placebo show a small effect of aspirin, averaging about 20% for reduction in all stroke

18. Anticoagulation Therapy

19. Dabigatran is not metabolized by cytochrome P450 isoenzymes, has no interactions with food, and also has a low potential for drug–drug interactions The elimination half-life is 12 to 14 hours, with clearance predominantly occurring via renal excretion of unchanged drug. New Anticoagulation Option • Anticoagulation: • RELY [Randomized Evaluation of Long-term anticoagulant therapY] trial • Dabigatran is a competitive, and reversible inhibitor of thrombin, inhibiting both thrombin activity and generation • peak plasma concentrations of dabigatran are reached approximately 2 hours after oral administration.

20. New medication for rhythm control • ATHENA (A Trial With Dronedarone to Prevent Hospitalizationor Death in Patients With Atrial Fibrillation) trial • Indirect meta-analysisby Piccini et al. Compared amiodarone with dronedarone in AF. • Patients treated with amiodarone, compared with dronedarone,were twice as likely to remain in sinus rhythm • However, amiodarone was associated with a trend toward greaterall-cause mortality and was associated with greater rates of adverse events requiringdrug discontinuation. • Analytical approach to compare 2 drugs thathave not been studied in a head-to-head randomized controlledtrial

21. New medication for rhythm control

22. Question 1 • A previously healthy 47-year-old woman presented 6 days ago with a complaint of palpitations of sudden onset. Her evaluation at that time included an electrocardiogram, which revealed atrial fibrillation (AF) with a ventricular response of 135 beats/min. She was late for an interview, and unfortunately she left the office before you were able to evaluate her. Her symptoms persisted without resolution until yesterday. She decided to return to your office out of fear of this happening again. Repeat EKG shows normal sinus rhythm. Her cardiac examination is unremarkable. She has no other medical problems and takes no medications. A transthoracic echocardiogram (TTE) is normal. Which of the following is the most likely classification of this patient's AF? ❏A. Permanent ❏B. Persistent ❏C. Recurrent ❏D. Isolated ❏E. Paroxysmal

23. Question 1 Key Concept/Objective:To understand the appropriate classification of AF • Answer: E • The ACC/AHA/ESC guidelines include the following categories: recurrent—more than one episode of AF has occurred; lone —AF occurring in a patient younger than 60 years who has no clinical or echocardiographic evidence of cardiopulmonary disease; valvular—AF occurring in a patient with evidence or history of rheumatic mitral valve disease or prosthetic heart valves is defined as valvular; paroxysmal—AF that typically lasts 7 days or less, with spontaneous conversion to sinus rhythm; persistent—AF that typically lasts longer than 7 days or requires pharmacologic or direct current (DC) cardioversion; permanent—AF that is refractory to cardioversion or that has persisted for longer than 1 year. Paroxysmal, persistent, and permanent AF categories do not apply to episodes of AF lasting 30 seconds or less or to episodes precipitated by a reversible medical condition. Reversible conditions include acute myocardial infarction, cardiac surgery, pericarditis, myocarditis, hyperthyroidism, pulmonary embolism, and acute pulmonary disease.

24. Question 2 • A 75-year-old woman with a history of symptomatic, recurrent, persistent nonvalvular AF comes to your office. She has been told that there are several options for the treatment of her AF. Which of the following is true regarding establishment and maintenance of normal sinus rhythm, as compared with pharmacologic rate control? ❏ A. Establishment and maintenance of sinus rhythm provides no survival advantage ❏ B. Establishment and maintenance of sinus rhythm reduces thromboembolic risk ❏ C. Establishment and maintenance of sinus rhythm improves the degree of symptomatic impairment ❏ D. Conversion to normal sinus rhythm is rarely needed for patients with unstable angina, acute myocardial infarction, heart failure, or pulmonary edema ❏ E. Answer choices B, C, and D are all true

25. Question 2 Key Concept/Objective:To understand that establishment and maintenance of sinus rhythm is not superior to ventricular rate control in patients with AF • Answer: A • Several trials compared restoration of sinus rhythm with control of ventricular rate in patients with AF. Evaluated outcomes included overall mortality, stroke, symptoms, and quality of life. Contrary to the expectations of many experts, maintenance of sinus rhythm provided no survival advantage and possibly a higher mortality when compared with ventricular rate control. Maintenance of sinus rhythm frequently requires the use of antiarrhythmic medications that may precipitate ventricular arrhythmias, bradycardia, and depression of left ventricular function. It was further theorized that maintenance of sinus rhythm would reduce rates of thromboembolism and the need for anticoagulation; however, trial results demonstrated no significant reduction in thromboembolic risk. Peak exercise capacity may improve with maintenance of sinus rhythm, but the two treatment strategies result in a similar degree of perceived symptomatic impairment. Nevertheless, ventricular rate control frequently is not feasible because of the complications that patients experience while in AF. AF often cannot be tolerated by patients with unstable angina, acute myocardial infarction, heart failure, or pulmonary edema.

26. Question 3 • An 81-year-old man with a history of symptomatic permanent AF presents to your office to discuss options for reestablishing sinus rhythm. He hopes to decrease his symptoms of dyspnea. In addition to AF, the patient has congestive heart failure and echocardiographically documented significant mitral regurgitation. Which of the following is a risk factor for cardioversion failure in this patient? ❏ A. Duration of AF of longer than 1 year ❏ B. Older age ❏ C. Left atrial enlargement ❏ D. Rheumatic heart disease ❏ E. All of the above

27. Question 3 Key Concept/Objective:To know the risk factors associated with failed synchronized DC cardioversion • Answer: E • Although success rates are high with DC cardioversion, a number of risk factors for cardioversion failure have been identified. These include longer duration of AF (notably, longer than 1 year), older age, left atrial enlargement, cardiomegaly, rheumatic heart disease, and transthoracic impedance. Pretreatment with amiodarone, ibutilide, sotalol, flecainide,propafenone, disopyramide, and quinidine have been shown to increase DC cardioversion success rates.

28. Question 4 • A 70 y/o AAF with DM type 2 is evaluated for dyspnea and fatigue. She has h/x of AF that has resulted in these symptoms in the past. She has had a successful cardioversion, most recently 2 years ago. She also has HTN, controlled with medications and mild LVD related to CAD and myocardial infarction. Her current medications include atenolol, lisinopril, ASA and insulin. Physical examination demonstrates an irregular irregular rhythm with a HR of 78 beats per minute. Blood pressure is 130/80mm Hg. The cardiovascular and pulmonary examinations are otherwise unremarkable. What medication should this patient receive AFTER cardioversion? ❏ A. ASA for 3 weeks only ❏ B. Warfarin for at least 4 weeks ❏ C. Plavix for 6 months ❏ D. Metoprolol for 1 week ❏ E. No additional medications are needed

29. Question 4 Key Concept/Objective:To know which anticoagulation is indicated with synchronized DC cardioversion • Answer: B • Patients with AF lasting more than 48 hrs or those with intracardiac thrombus should receive anticoagulation with warfarin, 3weeks before cardioversion and for at least 4 weeks afterwards. If the patient will get a TEE, they will need 48hrs of heparin followed by 4 weeks of amiodarone.

30. Question 5 • A 67 year old woman is admitted to the emergency room because of sudden onset of chest pain and rapid pulse. She has no history of similar occurrences. Physical examination reveals a pale diaphoretic woman in moderate respiratory distress. Her systolic blood pressure is palpable at 75mm Hg. Lungs show bibasilar crackles. There is no JVD and heart sounds are distant with a variable S1. An ECG showed AF with RVR.What is the most appropriate immediate therapy? ❏ A. Digoxin, 0.5mg intravenously ❏ B. Dialtiazem, 20 mg intravenously, followed by 10mg/h infusion ❏ C. Rapid infusion of 500ml of normal saline ❏ D. Direct-Curent Cardioversion ❏ E. Procainamide, 500mg IV over 20 min.

31. Question 5 Key Concept/Objective:To know the management of unstable patients with AF • Answer: D • Unstable patients with Atrial Fibrillation need cardioversion