Practical Rate and Rhythm Management of Atrial Fibrillation New Paradigm in Managing Atrial Fibrillation: A Campaign to Promote Optimal Patient Care Slide set developed by: Michael C. Delaughter, MD, PHD: EP-Cardiology PA Michael Eifling, MD: Texas Heart Institute at St. Luke’s Episcopal Hospital and Baylor University Rohit Mehta, MD: Sanger Heart and Vascular Institute

Management Principles of AF Cornerstones of AF Management Rate Control Rhythm Control Anticoagulation Control of symptoms Control of symptoms Prevention of thromboembolism Treatment or prevention of Tachycardia Induced Cardiomyopathy (CMP) Reduction in Hospitalizations Minimization of bleeding risk Therapeutic Goals Regardles of whether AF is paroxysmal or persistent, and whether rate or rhythm control is preferred, symptom control, avoidance of hospitalization and appropriate anticoagulation are key. Reduction in Hospitalizations 2 2

Rate versus Rhythm Control for AF The AFFIRM, RACE and AF-CHF trials have shown no mortality benefit from a rhythm control strategy compared to a rate control strategy. Therefore, a rate control strategy, without attempts at restoration or maintenance of sinus rhythm (SR), is reasonable in some patients with AF, especially those who are elderly and asymptomatic. If rate control offers inadequate symptomatic relief, restoration of SR may become a long-term goal. Restoration and maintenance of SR continues to be a reasonable treatment approach in many patients with AF. Rate versus Rhythm Control is a key decision point in AF management and should be driven by the patient’s symptoms and AAD / procedural risk. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. 3 3

Ventricular Rate Control Principles of a Rate Control Strategy: Adequate control of the ventricular response during AF can significantly improve symptoms and is critical to avoid tachycardia-mediated cardiomyopathy. Most patients managed using a rhythm control strategy also require medications for rate control. Rate control during atrial flutter tends to be more difficult than during AF. What is Adequate Rate Control? Control of the ventricular rate during AF is important both at rest and with exertion. No standard method for assessment of heart rate control has been established. Criteria for rate control vary with patient age but usually involve achieving ventricular rates between 60 and 80 bpm at rest and between 90 and 115 bpm during moderate exercise. For the AFFIRM trial, adequate control was defined as an average HR up to 80 bpm at rest and either an average rate up to 100 bpm during Holter monitoring with no rate above 100% of the maximum age-adjusted predicted exercise HR, or a maximum HR of 110 bpm during a 6-min walk test. In the RACE trial, rate control was defined as less than 100 bpm at rest. Only about 5%of patients from these trials required AV ablation to achieve HR control. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. 4

Ventricular Rate Control: Drugs to Control the Ventricular Response Beta blockers are the most effective drug class for rate control. Calcium channel antagonists (nondihydropyridine) are good choices for patients with asthma or COPD requiring beta agonist inhaler therapy. Digoxin provides relatively poor rate control during exertion and should be reserved for patients with systolic HF. Digoxin does not convert AF to SR and may perpetuate AF. Digoxin is marginally effective as a sole agent, but may prove useful in combination with beta blocker or calcium channel antagonists, particularly in hypotensive patients. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. with modifications. 5

Ventricular Rate Control: Drugs to Control the Ventricular Response A combination of a beta blocker and either a calcium channel antagonist or digoxin may be needed to control the HR. The choice of medication should be individualized and the dose modulated to avoid bradycardia. Beta blockers and calcium channel antagonists should be used cautiously in patients with HF. AV nodal blocking drugs at doses required to control the ventricular response can cause symptomatic bradycardia that requires pacemaker therapy. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. 6

Ventricular Rate Control: Drugs to Control the Ventricular Response Some antiarrhythmic drugs that are used to maintain sinus rhythm, such as sotalol, dronedarone, and amiodarone, also provide some control of the ventricular response when patients are in AF. Amiodarone should rarely be used for rate control because of its potential for toxicity. IV digoxin or nondihydropyridine calcium channel antagonists given to patients with AF and WPW may accelerate the ventricular response and are not recommended. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. 7

Ventricular Rate Control: AV Nodal Ablation Ablation of the AV conduction system and permanent pacing (the “ablate and pace” strategy) is an option for patients who have rapid ventricular rates despite maximum medical therapy and often yields remarkable symptomatic relief. There is growing concern about the negative effects of long- term RV pacing. Biventricular pacing, on the other hand, may overcome many of the adverse hemodynamic effects associated with RV pacing and is preferred when systolic dysfunction is present. Catheter ablation of the AV node should not be attempted without a prior trial of medication to control the rate. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed. with modifications. 8

CHADS2 Risk Stratification Scheme Anticoagulation HRS Education 3/25/2017 1:32 PM Risk Factors Score C Recent congestive heart failure 1 H Hypertension A Age 75 years D Diabetes mellitus S2 History of stroke or transient ischemic attack 2 It is critical to apply a risk scheme to quantify risk for stroke in AF. The CHADS2 scoring system is commonly used by several different guidelines and represents the current recommendation for stroke risk assessment of the ACC/AHA/ESC guidelines for the management of AF. Background: Several risk stratification schemes currently exist to aid physicians in selecting appropriate antithrombotic therapy for patients with AF. In order to assess the quality of such tools, 2 current and 1 new classification scheme (CHADS2) were assessed for their predictive value. The CHADS2 combined conclusions and recommendations from the AFI and the SPAF Investigators to create a scheme that assigned point values to comorbidities. The points are totaled to create the score. The CHADS acronym refers to the comorbidities it assesses and assigns a point value based on the risk factor. The C refers to recent CHF, the H stands for hypertension, A stands for age 75 or greater, and D is for diabetes, each of which receives 1 point. Two points are assigned for history of stroke or TIA. Patients are assessed for these risk factors and the total provides a guideline for risk and management of a patient. For example, a patient with recent CHF and diabetes would receive a score of 2 and would fall into the moderate-risk category. However, a patient who only has hypertension would have a score of 1. EP: Progress Indicators 1. Awareness of the existence of the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (knowledge) 2. Calculate a CHADS2 risk score for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (performance) Learning Objectives 1. Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) and calculate a CHADS2 risk score for such patients [Progress Indicators 1, 2] Instructional Objectives 1. Presented with clinical information for a patient with nonvalvular AF, participants will be able to identify the CHADS2 risk index as an appropriate assessment tool to determine stroke risk. 2. Given pertinent patient information, participants will be able to calculate a CHADS2 risk score for a patient with nonvalvular AF. CARD: Progress Indicators PCP: 1. Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) [Progress Indicator 1] 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] Rockson et al. J Am Coll Cardiol. 2004;43:929-935. 9

Maintenance of Sinus Rhythm: Principles of Antiarrhythmic Drug Therapy AF is a chronic disorder and is likely to recur in most patients without antiarrhythmic drugs (AADs). Pharmacological therapy is indicated in patients who can tolerate AADs and who have a reasonable chance to maintain sinus rhythm. Pharmacological therapy is indicated to suppress symptoms, improve exercise capacity, improve hemodynamic function, and prevent tachycardia-induced cardiomyopathy. The risk of stroke may not be reduced by suppression of AF. Before administering an antiarrhythmic drug, precipitants of AF such as hypertension, valve disease, CHF, hyperthyroidism, and OSA should be identified and corrected. Antiarrhythmic drug (AAD) choice is based on side-effect profiles and presence of structural heart disease, heart failure, or hypertension. Drug choice should be individualized and account for underlying renal and hepatic function. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed.

Maintenance of Sinus Rhythm: Principles of Antiarrhythmic Drug Therapy Drugs should be used to decrease the frequency and duration of episodes, and to improve symptoms. AF recurrence without symptoms is not indicative of treatment failure and does not necessitate a change in AAD therapy. An AAD should be abandoned when it does not result in symptomatic improvement or causes adverse events. Ensure normal electrolyte status and appropriate anticoagulation prior to starting antiarrhythmic drug therapy. Initiate AV nodal blockade prior to the use of antiarrhythmics such as flecainide that do not provide substantial AV node blockade. Initiate therapy at a low dose and titrate up as needed and after evaluating drug effects on ECG parameters. Knight, et al, Practical Rate and Rhythm Management of Atrial Fibrillation, January 2010 ed.

ACC/AHA/ESC Guidelines Maintenance of Sinus Rhythm in Specific Patient Populations No (or minimal) Heart Disease Hypertension Coronary Artery Disease Heart Failure Substantial LVH AmiodaroneDofetilide Flecainide PropafenoneSotalol Dofetilide Sotalol No Yes Flecainide PropafenoneSotalol Amiodarone AmiodaroneDofetilide CatheterAblation AmiodaroneDofetilide CatheterAblation CatheterAblation CatheterAblation CatheterAblation Amiodarone Calkins et al. HeartRhythm 2007 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46 12 12

Maintenance of Sinus Rhythm in Specific Patient Populations Suggested Scheme Including Dronedarone No (or minimal) Heart Disease Hypertension Coronary Artery Disease Heart Failure Substantial LVH Dofetilide Sotalol Dronedarone AmiodaroneDofetilide Flecainide Propafenone Sotalol Dronedarone No Yes Flecainide Propafenone Sotalol Dronedarone AmiodaroneDronedarone Amiodarone Dofetilide Catheter Ablation CatheterAblation CatheterAblation CatheterAblation Amiodarone Amiodarone Dofetilide CatheterAblation Abbreviation: LVH, left ventricular hypertrophy. Modified from Fuster, V. et al. J. Am. Coll. Cardiol. 48, e149–e246 (2006). 13 13

Rationale for Initial Trial of Medical Therapy The relative safety and efficacy of ablation vs. antiarrhythmic drugs has not been firmly established but large randomized trials are ongoing Ablation: Complication rate: 5.9% Single-procedure success rate without AADs: 57% Multiple-procedure success rate without AADs: 71% Multiple-procedure success rate with AADs: 77% AAD Therapy: Adverse event rate: 30% (common but less severe) Success rate: 52% Calkins et al. CircEP. 2009;2:349-361.

Atrial Fibrillation Ablation Candidates Anticoagulation HRS Education 3/25/2017 1:32 PM Symptomatic Paroxysmal or Persistent Atrial Fibrillation Second-line Therapy Failure of Class IC or Class III agent Intolerance to Medical Therapy, Refusal of Medical Therapy Other Considerations: Young patients with paroxysmal atrial fibrillation, in whom decades-long drug therapy is undesirable Congestive Heart Failure due to tachycardia-induced cardiomyopathy, in whom drug choices are limited by the presence of CHF 15

Atrial Fibrillation Ablation Candidates Limitations in Efficacy Longstanding Persistent Atrial Fibrillation (>1 year) Enlarged LA (>55 mm) Age > 70 years Left atrial or Left atrial appendage thrombus is an absolute contraindication to atrial fibrillation ablation. Calkins et al. HeartRhythm 2007 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46 16

Atrial Fibrillation Ablation Outcomes Definition of success includes: Freedom from symptomatic atrial fibrillation Freedom from all atrial fibrillation Facilitation of antiarrhythmic therapy Eradication of anticoagulant therapy Duration of Success: Freedom from atrial fibrillation at one year Freedom from late atrial fibrillation Most common accepted success definition Freedom from atrial fibrillation off antiarrhythmic therapy at one year Late recurrences: greater than 12 months Calkins et al. HeartRhythm 2007; HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46

Atrial Fibrillation Ablation Outcomes Blanking period of 2 months post ablation Early recurrence of AF events termed “early events” Minimum of symptomatic monitoring Suggested asymptomatic surveillance at 6 month intervals 30 day auto-triggered monitors Symptom triggered event monitors with weekly asymptomatic transmissions 24-72 hour Holter monitoring. Calkins et al. HeartRhythm 2007; HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46

Atrial Fibrillation Ablation Outcomes Paroyxsmal 70-80% success at freedom from atrial fibrillation at one year off anti-arrhythmic therapy. 30% of patients required 2 procedures to achieve this result. Most utilized pure-pulmonary vein isolation approach Persistent Similar success rates in persistent patients with similar end-point and need for repeat procedure More commonly requires substrate modification (targeting of CFAE) and linear ablation Long-Standing Persistent Utilizing stepwise approach (PV isolation Linear ablation CFAE), some studies have demonstrated 70-80% freedom from atrial fibrillation at one year off anti-arrhythmic therapy Calkins et al. HeartRhythm 2007; HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46

Atrial Fibrillation Ablation Outcomes Randomized Trials: Paroxysmal Atrial Fibrillation (Flecainide or Sotalol vs Ablation) One year freedom from atrial fibrillation (AF) 37% freedom from AF in anti-arrhythmic arm 87% freedom from AF in ablation arm Persistent Atrial Fibrillation (Ablation vs. Cardioversion) One year freedom from AF or atrial flutter 74% freedom from AF in ablation arm 58% freedom from AF in cardioversion arm Calkins et al. HeartRhythm 2007; HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation; 4: 1-46

Atrial Fibrillation Ablation Outcomes Randomized Trials: Paroxysmal or Persistent Atrial Fibrillation One year freedom from AF (ablation vs. anti-arrhythmic (AA) drug) 9% freedom from AF in the AA arm 56% freedom from AF in the ablation arm Paroxysmal Atrial Fibrillation One year freedom from AF (ablation vs anti-arrhythmic (AA) drug) 22% freedom from AF in AA arm 86% freedom from AF in ablation arm Stabile et al. European Heart Journal 2006; 27: 216-221

Atrial Fibrillation Ablation Outcomes Paroxysmal Atrial Fibrillation One year freedom from AF (ablation vs anti-arrhythmic (AA) drug) 22% freedom from AF in AA arm 86% freedom from AF in ablation arm Paroxysmal and Persistent Atrial Fibrillation One year freedom from AF (ablation vs. anti-arrhythmic (AA) drug) 7% freedom from AF in AA arm 75% freedom from AF in ablation arm 63% of AA treated patients crossed over Stabile et al. European Heart Journal 2006; 27: 216-221

Final Summary for AF Ablation Anticoagulation HRS Education 3/25/2017 1:32 PM Identifying appropriate ablation candidates Failing medical therapy Refusing medical therapy Need for symptoms Young patients  Differences in approach for paroxysmal and persistent patients Lesion set Utility of isuprel post ablation Likelihood of recurrence / need for additional procedures (see Cappato, Circulation, AF registry outcomes paper) Definition of success / likelihood of success Managing atypical flutter / need for confirmation of block across lines  Surgical based ablation Relative efficacy vs. catheter based Rationale / benefit of appendage ligation / resection Cox III – the “gold standard” Efficacy of other lesion sets, modalities (bipolar RF, cryo, HIFU) vs. Cox Take home point: AF will attain epidemic status over the next 50 years. 23