MANAGEMENT OF ATRIAL FIBRILLATION VINOD G V

Definitions Paroxysmal AF - self-terminating, usually within 48 h, may continue for up to 7 days. Persistent AF - when an AF episode either lasts longer than 7 days or requires termination by cardioversion. Long-standing persistent AF has lasted for ≥1 year when it is decided to adopt a rhythm control strategy. Permanent AF-DC version failed or not attempted Recurrent AF-has had 2 or more episodes

“lone AF” generally applies to young individuals under 60 y of age without clinical or echocardiographic evidence of cardiopulmonary disease including hypertension. have a favorable prognosis with respect to thromboembolism and mortality.

Haemodynamics Loss of atrial contraction A rapid ventricular rate An irregular ventricular rhythm Loss of mechanical AV synchrony affects ventricular filling esp. when left ventricle has reduced compliance.

3 objectives Rate control prevention of thromboembolism correction of the rhythm disturbance,

 Type and duration of AF  Severity and type of symptoms  Associated cardiovascular disease  Patient Age  Associated medical conditions  Pharmacological and nonpharmacological therapeutic options.

Rapid ventricular rate produce symptoms Tachycardia related cardiomyopathy

Rate control Strict rate control: Resting HR Moderate exercise Lenient HR Resting HR <100 RACE II (RAte Control Efficacy in permanent atrial fibrillation) trial did not identify a benefit of stringent rate control over lenient rate control therapy in 614 patients

Primary Outcomes Cardiac death CHF Stroke Systemic embolism Major bleed Syncope Sust VT Cardiac arrest Life threat compl of antiarrhythmic Pacemaker Secondary Outcomes Symptoms

Beta-Blockers useful in the presence of high adrenergic tone or symptomatic myocardial ischaemia Non dihydropyridine CCB-Diltiazem,verapamil Digoxin-effective at rest,not during exercise

Rhythm control

Theoretical Benefit of Rhythm Control Improved hemodynamics Relief of symptoms Improved exercise tolerance Reduced risk of stroke Avoidance of anticoagulants

Rhythm control Pharmacological Non pharmacological Cardioversion Catheter Ablation

Cardioversion in AF Pharmacological Electrical cardioversion

DC Cardioversion Delivery of an electric shock synchronised with the intrinsic activity of heart by sensing the R wave Successful cardioversion depends on Duration of AF Current density delivered to atrial myocardium

Joglar JA et al Am J Cardio 2000

Mittal S et al Ciculation 2000

Elhendy A et al Am J Cardio 2002

Pharmacological cardioversion Simple Less efficaious More effective in AF <7 day duration Problems of drug toxicity

AF lasting <1 wk – cardioversion -using oral flecainide, propafenone, dofetilide, and intravenous ibutilide. For longer duration- iv dofetilide( also amiodarone and ibutilide may be useful) Single oral dose of propafenone or flecainide – in recent onset AF (pill in the pocket)

2 strategies Oral warfarin with a therapeutic INR (2–3) for 3 to 4 weeks before cardioversion followed by continued warfarin thereafter Transesophageal echocardiography (TEE) and heparin immediately before cardioversion followed by oral warfarin thereafter. Left atria – stunning effect. So anticoagulation is to be continued for 4 wks

AF upto 7 days

AF >7 days

Pharmacological Rhytm control

Major Trials Comparing Rhythm Strategy and Rate Strategy Major trials include: – AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management ) – RACE (rate control versus electrical cardioversion) – PIAF (pharmacological intervention in AF) – AF-CHF Major overall findings : – Rhythm-control strategy was not superior to rate-control strategy in terms of morbidity/mortality – Appropriate choice of therapy should be based on each patient’s symptoms and disease – rate control, prevention of thromboembolism, and correction of the rhythm disturbance - these strategies are not mutually exclusive

AFFIRM : 5 Year Outcomes SurvivalRhythm controlRate control 1yr96 3yr8789 5yr7679 NO DIFFERENCE:Death, major bleed,disabling stroke,cardiac arrest Sinus rhythm maintained in only 63% of rhythm control group

AFFIRM Trial No survival advantage to rhythm control. Rhythm control patients were more likely to be hospitilized with adverse drug effects. Both groups had similar stroke risk (1% per yr) –Majority of strokes when warfarin stopped or INR subtherapeutic –Warfarin required long term even if sinus rhythm restored Torsades, bradycardic arrest more common with rhythm control.

Attempts at restoration of sinus rhythm not always successful –AFFIRM Trial: only 63% of “rhythm control” group were in sinus rhythm –Antiarrhythmics used to maintain sinus rhythm associated with a 25-50% annual failure rate. Long term anticoagulation not mandated in the “rhythm control” group –Those in afib at risk for stroke Medications used to maintain sinus rhythm risk of proarrhythmia and other toxicity

Vernakalant Acts preferentially in atria Blocking several ion channels Prolongation of atrial refractoriness Rate dependent slowing of atrial conduction Little impact on ventricular repolarization Pharmacological cardioversion of AF <7 days or <3days for patients after cardiac surgery

AVRO Double-blind,active-controlLed -i.v. amiodarone N=232 Vernakalant n = 116, Amiodarone n = 116 Hypertension(71.6%) ischaemic heart disease(22.4%) myocardial infarction (8.2%) heartfailure(19.8%)(NYHA I- 45.7%, NYHA54.3%) valvular heart disease, 6.9% AF 3–48 h (median 17.7 h) Time to conversion 11m Conversion to SR- 51.7% vs. 5.2% P < Reduction in symptoms at 2 h reported by 53.4% patients in the vernakalant groupvs. 32.8% in the Amiodarone group P =

“Pill in the Pocket” strategy Preferred in – Paroxysmal AF with no structural heart disease – Self administration of a single oral dose of drug shortly after the start of palpitations – Decrease hospital visits Propafenone mg Flecainide mg

Anti-arrhythmic drugs for maintaining sinus rhythm

Selection of specific agent depends on underlying cardiac disease

CATHETER ABLATION IN AF

Factors Factors that trigger Factors that perpetuate Triggering foci of rapidly firing cells within the sleeve of atrial myocytes extending into the pulmonary veins - shown to be the underlying mechanism of most paroxysmal AF

When to consider ablation? Antiarrhythmic therapy ineffective Antiarrhythmic therapy not tolerated Symptomatic afib

The stage of atrial disease ( AF type, LA size, AF history) The presence and severity of underlying cardiovascular disease Potential treatment alternatives (antiarrhythmic drugs, rate control) Patient preference

Anatomic ablation Electrogram guided ablation

Anatomic Carto Map of Lett atrium ablation points

Ablation may be a first strategy Patient very symptomatic in AF and refuses antiarrhythmic drug therapy Young patient whose only effective antiarrhythmic drug is amiodarone Patient with significant bradycardia for whom antiarrhythmic drug therapy will require pacemaker

Results Difficult to interpret –Success rate Optimal patient: –single procedure % –Multiple procedures 80 – 90% –Poor patient (eg 3 years persistent afib, sig enlarged LA –Best success with paroxysmal and healthy heart –Least success with chronic and diseased left atrium –May recur despite initial success –May recur without symptoms Ultimate goal: Rhythm control without toxic antiarrhythmics

Complication rate 1-5% –Tamponade – atrial perforation –TIA, stroke –Major bleed –Creation of atrial flutter (up to 8%) –Vascular access complications –Pulmonary vein stenosis (lower incidence than initial) –Aorto-esophageal fistula –Fatal 1/1000 Lengthy procedure –4-5 hours

Risk factors for recurrence of afib Long-term persistent afib Valvular heart disease Dilated cardiomyopathy

Anti Thrombotic therapy

Risk stratification CHADS2 –Congestive heart failure - 1pt –Hypertension - 1pt –Age > pt –Diabetes - 1pt –Stroke or TIA - 2 pts –0 points – low risk ( strokes per 100 patient years) –1point– moderate risk ( strokes per 100 patient years) –> 2 points – high risk ( strokes per 100 patient years)

CHA 2 DS 2 -VAS C

Anticoagulation strategy CHADS2 score 0 No anti thrombotic therapy CHADS2 score 1 Aspirin mg daily Oral anti coagulation CHADS2 score 2 Oral anti coagulation

Anti thrombotic therapy VKA eg: warfarin Antiplatelets eg aspirin,clopidogrel Newer oral anti coagulants Direct thrombin inhibitor-Dabigatran Fa Xa inhibitors-Apixaban,Rivaroxaban

Warfarin Effective Reversible Inexpensive Slow onset of action Regular monitoring Food interraction Medication interraction Difficult titration-regular dose adjustments

Aspirin

Clopidogrel + Aspirin ?

Aspirin: stroke 3.4% per year major bleed 1.27% per year Aspirin + clopidogrel: stroke 2.4% per year major bleed 2.0% per year

New anticoagulants Short half life – less bleeding Lack of need for routine monitoring Generally safer than warfarin –No antidote Cost of medication –Overall cost of care

Apixaban (Aristotle trial) Twice daily: 5mg BD Less hemorrhagic stroke than warfarin Similar reduction in ischemic stroke Less bleeding than warfarin Lower overall mortality No routine lab testing No reversal –Half life 8-15 hours

Dabigatran(RELY trial) Dabigatran 110 mg twice daily –Equal to warfarin in stroke prevention Warfarin 1.69%/yr – dabigatran (110mg) 1.53%/yr –Less bleeding than warfarin Warfarin 3.36%/year – dabigatran (110mg) 2.71%/yr Dabigatran 150 mg twice daily –More effective than warfarin in stroke prevention Dabigatran (150mg) 1.11%/yr –Equivalent bleeding to warfarin less hemorrhagic stroke than warfarin

Rivaroxaban (Rocket AF trial) Once daily: 20 mg Less hemorrhagic stroke than warfarin Similar reduction in ischemic stroke Less bleeding than warfarin No routine lab testing No reversal –Half life 5-9 hours Discontinuation : increased stroke

CHADS2 score includes all except 1.TIA 2.Age > 60 yrs 3.DM 4.Congestive heart failure

55 yr old man with AF, no h/o HTN,DM,no structural heart disease TRUE regarding antithrombotic therapy 1.Aspirin 150 mg OD 2.Warfarin 2mg 3.Dabigatran 150 mg BD 4.No antithrombotic therapy needed

30 yr old patient presented to emergency department with 2hr h/o palpitation,ECG showing wide complex irregular tachycardia rate 200/min preferred method of treatment 1.IV Verapamil 2.IV Diltiazem 3.IV Digoxin 4.IV Procainamide

Drug used in “pill in the pocket strategy” 1.Sotalol 2.Propafenone 3.Ibutalide 4.procainamide

True about Dabigatran except 1.RE-LY trial evaluated dabigatran 2.Two doses were evaluated in RE-LY trial 3.Rate of haemorragic stroke more compared to warfarin 4.Dose adjustment needed in CKD

CHA 2 DS 2 VASc score includes all except 1.Age yrs 2.Male sex 3.Atherosclerotic plaque in aorta 4.HTN

Drug prefered for maintainance of sinus rhythm in structurally abnormal heart is 1.Sotalol 2.Betablockers 3.Amiodarone 4.Ibutalide

Rivaroxaban true except 1.Rivaroxaban better than warfarin in reducing stroke in AF 2.20 mg twice daily 3.Less haemorrhage than warfarin 4.Evaluated in ROCKET AF trial

VERNAKALANT all are true except 1.Acts preferentially in atria 2.Causes significant QT prolongation 3.Used in post operative AF conversion 4.Contraindicated in heart failure

Apixaban TRUE EXCEPT 1.Direct thrombin inhibitor 2.Evaluated in ARISTOTLE trial 3.Cause less haemorrhage than warfarin 4.Non inferior to warfarin in stroke prevention