Atrial Fibrillation Rate vs Rhythm control Which is better ? Dwayne Campbell, MD

Disclosure Medtronic Milestone Pharmaceuticals, Inc. National Institutes of Health Employee-Iowa Heart Center/Mercy-Des Moines

Objective Review goals of Atrial fibrillation management Compare rate vs rhythm control management Strategy in achieving those goals Review current guidelines for afib management

Epidemiology and Prognosis Most common arrhythmia >80% of individuals are > 65yo 1/3 of hospitalizations for arrhythmias 2.3 million people in North America 70,000 strokes/yr due to AF 1990 – 2005 admissions increased 66% $1 billion spent yearly on post- op AF JACC 2004; 43:1001-1003

Mortality and AF Am J Cardiol 2001; 87:346 Statistics: AF increases the risk of mortality in men (1.5 times) and women (1.9 times). AF increases the risk of CVA (stroke) five-fold. AF causes an estimated 75,000 strokes a year in the USA In the US, about 23% of all strokes can be attributed to AF (percentage increases dramatically with advancing age) Am J Cardiol 2001; 87:346

Classification Paroxysmal Persistent Long- Standing persistent Spontaneous termination Last < 7 days Usually < 48 hrs Persistent No spontaneous termination Lasting > 7 days Long- Standing persistent >12 months Non valvular >AF in the absence of rheumatic mitral stenosis, a mechanical or bio prosthetic heart valve, or mitral valve repair

Management strategy Rate control Rhythm control HR control with no commitment to restore NSR Drugs or pacer Rhythm control Attempt restoration and maintenance of NSR cardioversion or catheter ablation Both strategies require anticoagulation to prevent thromboembolism

CHA2DS2-VASc Score Risk factor Score Congestive heart failure/LV 1 Hypertension Age ≥75 years 2 Diabetes mellitus Stroke/TIA/thromboembolism Vascular disease Age 65-74 years Sex category (ie, female sex) Maximum score 9 * Prior MI, PAD, aortic plaque. Actual rates of stroke in contemporary cohorts may vary from these estimates Camm AJ et al: Eur Heart J 2010;31:2369-2429

Ultimate Goal of Management Improve Mortality /Morbidity Decrease incidence of of Thromboembolic events Improve quality of life

4060 patients - randomized to rate or rhythm control strategies Digoxin, calcium channel blocker, and/or beta-blocker were used for rate control(2027 patients) Electrical cardioversions, class IA, IC, and III drugs to rhythm-control arm (2033 ) Oral anticoagulation adjusted to maintain INR of 2.0 to 3.0 Could be stopped if sinus rhythm > 4 weeks

AFFIRM Trial P 0.08 N Engl JMEd 2002;3479230:1825 p value 0.08 deaths primarily due to cancer . another amiodarone trial with similar findings. talk about AF CHF trial no mortality benefit (thought due to excellent control of comorbid conditions. does not say rate controls is better.

Major trials comparing rhythm to rate controls PIAF-Pharmacological Intervention in Atrial Fibrillation (2000) STAF - Strategies of Treatment of Atrial Fibrillation study(2003) RACE-Rate Control vs Electrical cardioversion for persistent AF(2002) AFFIRM-AF follow–up investigation of rhythm management (2002) HOT CAFÉ- - How to Treat Chronic Atrial Fibrillation(2004) AF CHF-Atrial Fibrillation and Congestive Heart Failure(2007) J RHYTHM- Japanese Rhythm Management Trial for AF(2009)

Mortality de Denus et al. Arch intern Med. 2005;185:258

Thomboembolic Events de Denus et al. Arch intern Med. 2005;185:258

Quality of Life Measures Singh et al. J Am Coll Cardiol 2008;48:721-30

“Nature has equipped the human heart with a complex electrical system for the purpose of coordinated propulsion of blood under a variety of physiologic conditions. Considerable effort is expended by the heart to maintain sinus rhythm. Cardiac electrophysiologists…are frustrated by the conundrum that atrial fibrillation is associated with increased morbidity and mortality, yet attempts to prove that a strategy to maintain nature’s rhythm has a favorable effect on patients have been met with one setback after another. Cain ME. Rhythm control in atrial fibrillation—one setback after another New Engl J Med. 2008;258-2725-

So why no difference between strategies ? limitations of anti-arrhythmic drugs all proarrythmic(increase mortality with SHD end organ toxicity poor long term efficacy treatment palliative not curative subjective adverse events limitations of the trials waldos idealide slide

Major trials comparing rhythm to rate controls

Rhythm controlled preferred Persistent symptoms despite rate controls Inability to maintain adequate rate controls First episode of atrial fibrillation Younger patients Sign symptoms of left ventricular dysfunction Patient preference

Rhythm Control Strategy 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation Rhythm Control Strategy Strategies for rhythm control in patients with paroxysmal* and persistent AF.† *Catheter ablation is only recommended as first-line therapy for patients with paroxysmal AF (Class IIa recommendation). †Drugs are listed alphabetically. ‡Depending on patient preference when performed in experienced centers. §Not recommended with severe LVH (wall thickness >1.5 cm). ‖Should be used with caution in patients at risk for torsades de pointes ventricular tachycardia. ¶Should be combined with AV nodal blocking agents. AF indicates atrial fibrillation; AV, atrioventricular; CAD, coronary artery disease; HF, heart failure; and LVH, left ventricular hypertrophy. Craig T. January et al. Circulation. 2014;130:e199-e267 .

PAF – 198 patients JACC 2006; 48 (11):2340-2347

Rate control preferred AF duration > one year Increased left atrial size>4.5cm Underlying cause of AF that has not been treated Age >65y Patient preference

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation Rate control strategy Approach to selecting drug therapy for ventricular rate control.* *Drugs are listed alphabetically. †Beta blockers should be instituted following stabilization of patients with decompensated HF. The choice of beta blocker (eg, cardioselective) depends on the patient’s clinical condition. ‡Digoxin is not usually first-line therapy. It may be combined with a beta blocker and/or a nondihydropyridine calcium channel blocker when ventricular rate control is insufficient and may be useful in patients with HF. §In part because of concern over its side-effect profile, use of amiodarone for chronic control of ventricular rate should be reserved for patients who do not respond to or are intolerant of beta blockers or nondihydropyridine calcium antagonists. COPD indicates chronic obstructive pulmonary disease; CV, cardiovascular; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; and LV, left ventricular. Craig T. January et al. Circulation. 2014;130:e199-e267 .

Adequate rate control HR<110 at rest mean rate in affirm 78 race 1 84 race ii lenient 94 strict 76 guide lines resting hr<110 check guidelines Kaplan-Meier estimates of the cumulative incidence of the primary outcome (composite of: death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events) comparing strict versus lenient rate control

Conclusion Due to limitation of current medical therapy a rate control strategy has not been shown to be inferior to a rhythm control strategy Unclear what is the best option is for younger patients Ablation is more effective in maintaining NSR than AAD but Data on whether or not this translates to improved mortality is Pending (CABANA Trial)

Management Rate control Prevention of thromboembolism Conversion to NSR – always try Management Pattern of presentation – persistent, paroxysmal, permanent Underlying conditions Restoration and maintenance of NSR HR control and anticoagulation

Prevalence of sinus rhythm (SR) at one year Prevalence of sinus rhythm (SR) at one year. Patients are included only if they were randomized one year or more before the termination of the substudy. Black bars= SR, another drug, ± cardioversion; hatched bars= SR, on drug #1, cardioversion; white bars= SR, on drug #1, no cardioversion. Maintenance of sinus rhythm in patients with atrial fibrillation ☆: An AFFIRM substudy of the first antiarrhythmic drug The AFFIRM First Antiarrhythmic Drug Substudy Investigators, e1Journal of the American College of Cardiology Volume 42, Issue 1, 2 July 2003, Pages 20–29

Kaplan-Meier estimates of the cumulative incidence of the primary outcome (composite of: death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events) comparing strict versus lenient rate control

Who Gets AF? Both genders get AF but it is more dangerous for women Men with AF have 1.5 times greater risk of death than men without AF Women with AF have 1.9 x greater risk of death than women without AF Structural heart disease, age, DM, CHF, HTN, OSA, COPD, TSH, familial, CAD Circulation 1998; 98 (10): 946-52

Impact of OSA on Atrial Fibrillation 720 consecutive pts Treated OSA was > 4hrs CPAP AF recurrence seen in: - 51% OSA vs 30% no OSA (p<0.0001) 68% untreated vs 35% treated (p<0.0001) Neilan G et al. Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation. JAHA 2013.

Atrial Fibrillation Definition Atrial fibrillation (AF) is an atrial tachyarrhythmia Uncoordinated atrial activation with lack of atrial mechanical function AF impulses usually generate in the atria and in the pulmonary veins