Understanding Atrial Fibrillation Management Roy Lin, MD
Disclosure None
Definition of atrial fibrillation Atrial fibrillation is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of mechanical function. ECG shows, rapid oscillations, or fibrillatory waves that vary in amplitude, shape, and timing, replace consistent P waves, and there is an irregular ventricular response.
Atrial fibrillation
Learning Objectives Understanding atrial fibrillation Reducing thromboembolic risk Understanding rate and rhythm control
Consequence of AF Thromboembolism Stroke: 4.5 risk Microemboli: cognitive function Prothrombotic state Mortality 2 risk independent of comorbid CV disease Sudden death in HF and HCM Hospitalizations Most common arrhythmia requiring hospitalization 2-3 risk for hospitalization Quality of life Palpitations, dyspnea, fatigue, exercise tolerance Impaired hemodynamics Loss of atrial kick Irregular ventricular contractions Heart failure Tachycardia-induced cardiomyopathy AF is an enormous contributor to the growing cost of medical care Estimated US cost burden: $15.7 billion
Prevalence of AF
Clinical features
Workup Identify symptom frequency, severity, and duration Identify underlying causes Structural heart disease Other causes and risk factors
Risk factors for AF
Workup Laboratory Serum electrolytes and TSH Renal and hepatic function Fecal occult stool test Transthoracic echocardiography Identify structural heart disease Identify cardiomyopathy Transesophageal echocardiography if indicated
Extracardiac Factors: Hypertension Obesity Sleep apnea Hyperthyroidism Alcohol/drugs Atrial Structural Abnormalities: Fibrosis Dilation Ischemia Infiltration Hypertrophy Inflammation Oxidative stress Atrial tachycardia remodeling AF RAAS activation Genetic Variants: Channelopathy Cardiomyopathy Atrial Electrical Abnormalities: Heterogeneity Conduction Action potential duration/refractoriness Automaticity Abnormal intracellular Ca ++ handling Autonomic nervous system activation
Summary AF is the most common cardiac arrhythmia Establishing the diagnosis and symptoms Some patients may be asymptomatic Identify risk factors Assess for underlying disorders or contraindications to therapies Imaging to look for structural heart disease
Goals of therapy To prevent thromboembolism Stroke is the most important event To reduce symptoms Mild to disabling symptoms To prevent heart failure Persistent tachycardia can lead to cardiomyopathy
Stroke with AF Stroke is the most common and devastating complication AF increase stroke risk 5 fold Stroke risk persist even in asymptomatic AF Risk of stroke is the same in paroxysmal or sustained Without AF < 60 years: 0.5% > 80 years: 3% With AF < 60 years: 3% > 80 years: 30%
Stroke with AF N = 1061 admitted with acute ischemic stroke 20.2% had AF Bedridden state With AF - 41.2% Without AF - 23.7% Odds ratio for bedridden state following stroke due to AF = 2.23 (P < 0.0005) No Difference in Risk with Paroxysmal vs Persistent AF Dulli DA et al. Neuroepidemiology. 2003;22:118-23.
Thromboembolic risk
Thromboembolic risk Nonvalvular atrial fibrillation When the risk for thromboembolism exceeds the risk for serious bleeding from anticoagulation When the CHA2DS2-VASc is 2 Guidelines recommend anticoagulation for all patients with documented atrial fibrillation (symptomatic or asymptomatic) and 2 CHA2DS2-VASc risk factors (I) Anticoagulation considered reasonable but not mandatory when the score is 1 (IIb)
Antithrombotic Agents Aspirin 81 mg oral daily Warfarin Direct acting oral anticoagulation (DOACs) Dabigatran Rivaroxaban Apixaban Edoxaban
Challenges With DOACs No validated tests to measure anticoagulation effect No established therapeutic range Assessment of compliance more difficult than with vitamin K antagonists No antidote for most agents Balancing cost against efficacy Lack of head-to-head studies comparing new agents Lack of evidence in use for ESRD Not for valvular AF, mechanical heart valves
HAS-BLED
Avoiding bleeding risk Odds Ratio 15.0 10.0 5.0 Stroke Intracranial Hemorrhage 1.0 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 INR Fuster et al. J Am Coll Cardiol. 2001;38:1231-1266.
Avoiding bleeding risk Elderly patients and those with cerebrovascular disease are at increased risk Keep INR 3 Combination of warfarin and aspirin should be used with special caution in elderly patients and those with cerebrovascular disease Modest blood pressure-lowering profoundly reduces CNS bleeding Closure of the left atrial appendage is an alternative for thromboembolic protection
High risk patient intolerant to OAC CHA2DS2-VASc of 3 or CHADS2 2
Summary Stroke associated with AF are more debilitating Balance between stroke and bleeding risk CHA2DS2-VASC score: to select patients for anticoagulation Closure of the left atrial appendage is an alternative for thromboembolic protection
AF Management ANTITHROMBOTIC RX AND RHYTHM CONTROL OR RATE CONTROL
Rate and Rhythm Control
Rate and Rhythm Control Rate control Rest and exertion control of ventricular response Rhythm control Attempts restoration and maintenance of SR Rate control required as needed Difficult to switch from rate to rhythm control as duration of AF becomes longer ANTICOAGULATION NEEDED for either strategy
AFFIRM: All-Cause Mortality 30 25 Rate Rhythm Mortality, % 20 15 10 p=0.078 unadjusted p=0.068 adjusted 5 0 Rhythm N: 0 1 2 3 4 5 Time (years) 2033 1932 1807 1316 780 255 Rate N: 2027 1925 1825 1328 774 236 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
Limitation of rate control Mean ages in AFFIRM and RACE were 70 and 68 years, respectively Limited symptom/frequency of study patients Cessation of anticoagulant therapy four weeks after documentation of SR, leading to a higher rate of stroke. Antiarrhythmic drugs in AFFIRM was associated with a significant increase in mortality Data were largely gathered before catheter ablation was common
Rate control plus anticoagulation preferred No AF symptoms Long AF Hx More SHD Toxicity Risk Greater risk of proarrhythmia Rhythm control preferred Greater AF symptoms AF compromising LV function Symptoms despite rate control Younger age No or lesser SHD Rx option of class IC AAD In anticoagulation candidates, continue anticoagulation indefinitely
Case #1 54 year old male New onset of palpitation that started 2 hours ago Atrial fibrillation with ventricular rate of 130-150 bpm. BMI of 35 kg/m^2 Symptoms of sleep apnea
What s next? PO metoprolol was given with improved heart rate and symptom What s next?
What to do next? 1. Hospitalize 2. DC Cardioversion +/- TEE 3. IV Amiodarone 4. IV Ibutilide 5. Come back in 24 hrs and reevaluate
When to cardiovert Most patients do not require immediate cardioversion Cardioversion can be useful in select circumstances Decompensated HF, severe angina, acute infarction, hypotension, high risk for acute stroke Patients with atrial fibrillation and extreme tachycardia, for example, with Wolff- Parkinson-White syndrome
When to hospitalize Uncertain or unstable underlying arrhythmia Acute MI, altered mental status, decompensated HF, or hypotension Intolerable symptoms despite hemodynamic stability For elective cardioversion when a monitored, outpatient setting is not available For acute anticoagulation if very-high risk for stroke Telemetry monitoring during initiation of certain drugs
< 24 hours duration Minimally symptomatic with rate control Observe for another 24 hours (may be paroxysmal) Anticoagulate if indicated
Case #1 Patient returns to clinic the next day AF rhythm heart rate 90-100 s bpm TTE unremarkable, TSH wnl
< 48 hours but >24 hours Cardiovert if SR is desirable Most patients with new onset atrial fibrillation regardless of age Rate control and anticoagulation if appropriate
Rhythm control 48 hours or unknown duration anticoagulate for at least 3 weeks before and 4 weeks after cardioversion <48 hours and high stroke risk anticoagulate before or immediately after cardioversion followed by long-term anticoagulation <48 hours and low stroke risk, may be considered for cardioversion with or without anticoagulation (IIB)
Cardioversion Electrical cardioversion Rapid and immediate Drug therapy Side effects should guide choice of antiarrhythmic drugs Serum potassium should be >4.0, serum magnesium >1.0, and ionized calcium levels >0.5 mg/dl
Rhythm control Pharmacologic cardioversion AF < 1 week flecainide, ibutilide, propafenone, dofetilide, amiodarone AF > 1 week dofetilide, amiodarone
Successful cardioversion Sleep study Weight loss Alcohol reduction Gami, et al. JACC 2007;49:565-71
Case 2 82 year old female with long history of permanent atrial fibrillation on anticoagulation Routine office visit notes fatigued in the last year Heart rate of 110 s bpm
What s next Comprehensive assessment Uptitration of rate control
RACE II 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. No difference between Lenient and Strict Rate Control If lenient rate control: check serial echo for declining LV function NEJM April 15, 2010, No. 15, Vol 362: 1363-1373
Rate control Drug therapy to control ventricular rate in all patients, even if rhythm control is ultimately the goal Rate <80 bpm (IIa) Rate <110 bpm if asymptomatic and normal LVEF (IIb) CCB should not be used in decompensated HF (Class III) AV node and pacemaker if rate control not achievable (IIa)
Rate control To decrease AV nodal conduction (first-line): β- blockers, nondihydropyridine calcium-channel antagonists To slow conduction through AV node (but not first-line monotherapy for rate control): digitalis, amiodarone To reduce ventricular response if other agents have failed: amiodarone (difficult to justify due to associated toxicities)
Atrial Fibrillation No Other CV Disease Hypertension or HFpEF LV Dysfunction or HF COPD Beta blocker Diltiazem Verapamil Beta blocker Diltiazem Verapamil Beta blocker Digoxin Beta blocker Diltiazem Verapamil Amiodarone
Case: 3 60 year old female paroxysmal atrial fibrillation, third reoccurrence symptomatic AF rhythm this month Currently on beta blocker: HR 80 bpm Still feels terrible Otherwise healthy
Rhythm control Class Ic drugs, such as flecainide and propafenone, are useful in patients without significant structural heart disease Other class I drugs are used infrequently because of noncardiac side effects and concern for proarrhythmia Class III drugs, such as sotalol and dofetilide, can prolong the QT interval and cause torsades de pointes Amiodarone: permanent liver and lung toxicity is dose- and duration-dependent Dronedarone: similar in structure to amiodarone but without iodine and with less antiarrhythmic efficacy Contraindicated for decompensated CHF and for permanent atrial fibrillation
Rhythm control Proarrhythmia: VT with Flecainide, Propafenone in LVH, CAD, Decreased EF Torsades in Dronedarone, Sotalol, Dofetilide Organ Toxicity: Amiodarone, procainamide, quinidine Organ Toxicity: Lupus, agranulocytosis, thrombocytopenia, optic neuritis, pulmonary fibrosis, hepatitis, etc.
Expectations of rhythm control in AF Complete suppression Best, but AF recurrence not uncommon Recurrence, per se, is not failure of therapy Frequency of recurrence More realistic measure of efficacy May vary from patient to patient
Maintenance of Sinus Rhythm No (or Minimal) Heart Disease Hypertension Coronary Artery Disease Heart Failure Dronedarone Flecainide Propafenone Sotalol No Substantial LVH Yes Dofetilide Dronedarone Sotalol Amiodarone Dofetilide Amiodarone Dofetilide Catheter Ablation Dronedarone Flecainide Propafenone Sotalol Amiodarone Amiodarone Catheter Ablation Catheter Ablation Amiodarone Dofetilide Catheter Ablation Catheter Ablation In some patients, especially young individuals with very symptomatic AF, ablation may be preferred over years of drug therapy. *
Catheter AF Ablation Symptomatic AF refractory or intolerant to at least 1 class I or III AAD (I) Selected symptomatic patients with HF and/or reduced ejection fraction Discontinuation of anticoagulation is not an indication for ablation
Conclusion AF is the most common arrhythmia Take the opportunity to address and treat underlying risk factor For every patient with AF, decisions need to be made regarding (1) antithrombotic therapy, (2) rate control, and/or rhythm control Anticoagulation is essential in AF patients with risk markers, regardless of any restoration of SR New agents and procedures may provide antiarrhythmic and antithrombotic options with improved outcomes for managing AF