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 -60-80 Moderate exercise 90-110• 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 deathCHFStrokeSystemic embolismMajor bleedSyncopeSust VTCardiac arrestLife threat compl of antiarrhythmicPacemaker

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 alAm 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

Survival Rhythm control Rate control

1yr 96 96

3yr 87 89

5yr 76 79

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 <0.0001• Reduction in symptoms at 2 h reported by 53.4%

patients in the vernakalant groupvs. 32.8% in the Amiodarone group P = 0.0012

“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 visitsPropafenone 450-600mgFlecainide 200-300mg

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 60 - 80%– 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 afibValvular heart diseaseDilated cardiomyopathy

Anti Thrombotic therapy

Risk stratification

• CHADS2 – Congestive heart failure - 1pt– Hypertension - 1pt– Age > 75 - 1 pt– Diabetes - 1pt– Stroke or TIA - 2 pts

– 0 points – low risk (1.2-3.0 strokes per 100 patient years)– 1point– moderate risk (2.8-4.0 strokes per 100 patient years)– > 2 points – high risk (5.9-18.2 strokes per 100 patient years)

CHA2DS2-VASC

Anticoagulation strategy

• CHADS2 score 0 No anti thrombotic therapy• CHADS2 score 1 Aspirin 75-325 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 except1.TIA2.Age > 60 yrs3.DM4.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 OD2.Warfarin 2mg 3.Dabigatran 150 mg BD4.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 Verapamil2.IV Diltiazem3.IV Digoxin4.IV Procainamide

• Drug used in “pill in the pocket strategy”1.Sotalol2.Propafenone3.Ibutalide4.procainamide

• True about Dabigatran except1.RE-LY trial evaluated dabigatran2.Two doses were evaluated in RE-LY trial3.Rate of haemorragic stroke more compared to

warfarin4.Dose adjustment needed in CKD

• CHA2DS2 VASc score includes all except1.Age 65-74 yrs2.Male sex3.Atherosclerotic plaque in aorta4.HTN

• Drug prefered for maintainance of sinus rhythm in structurally abnormal heart is

1.Sotalol2.Betablockers3.Amiodarone4.Ibutalide

Rivaroxaban true except1.Rivaroxaban better than warfarin in reducing

stroke in AF 2.20 mg twice daily3.Less haemorrhage than warfarin4.Evaluated in ROCKET AF trial

• VERNAKALANT all are true except1.Acts preferentially in atria2.Causes significant QT prolongation3.Used in post operative AF conversion4.Contraindicated in heart failure

• Apixaban TRUE EXCEPT1.Direct thrombin inhibitor2.Evaluated in ARISTOTLE trial3.Cause less haemorrhage than warfarin4.Non inferior to warfarin in stroke prevention