Atrial fibrillation...rx

ATRIAL FIBRILLATIONDr. Nagula Praveen

Management

GOALS: Prevention of stroke Prevention of tachycardia induced

cardiomyopathy Symptom relief Improved survival Primary prevention

Three strategies

Rate control – in all patients with AF Rhythm control – in selected patients with AF Prevention of thrombo embolism

Management

MEDICAL 1.ANTIARRHYTHMIC DRUGS 2.AV NODAL BLOCKING DRUGS 3.ACEI 4.ARBS 5.STATINS 6.FATTY ACIDS 7.STEROIDS SURGICAL —MAZE PROCEDURE ABLATION PACEMAKER ANTI THROMBOTIC TREATMENT

Anticoagulation

Risk stratification Peri cardioversion

RISK FACTORS Highest risk of stroke >6% /yr Valvular 15- 20 times the nonvalvular Prosthetic valves 2.5-3.5 MVR – 2.0- 3.0 previous h/o TIA/stroke

Intermediate risk factors ---3—5 % /yr CHA2DS2VASc score One intermediate risk factor present HTN Diabetes Age

• Lone AF lowest risk < 2% yr

FRAMINGHAM RISK SCORE

CHA2DS2VASc SCOREFACTOR POINTS/MAX SCORE---

9

1. C CONGESTIVE HEART FAILURE

1

2.H HYPERTENSION 1

3. A AGE> 75 YRS 2

4. D DIABETES 1

5. S2 PRIOR STROKE/TIA 2

6.V VASCULAR DISEASE 1

7.A AGE 65-74 1

8.Sc SEX CATEGORY(F) 1

THERAPY ACCORDING TO RISK FACTORS

Pericardioversion

AF ---- mechanical stasis in atria, atrial appendage.---pro inflammatory state--- pro thrombotic state.

Unstable thrombus – dislodge on contraction. Atrial mechanical function lags behind electrical

function. Atrial mechanical stunning --- 4 weeks

JACC 1989 If not risk of event – 5%

If > 48 hrs Empiric anticoagulation for 3 weeks. Short term anticoagulation : TEE guided

Why 3 weeks – organisation of thrombus Warfarin?--- target 2.5 Do weekly INR before cardioversion. Low INR more events

JACC;2002;40(5)

Heparin followed by TEE – thrombus present --- warfarin for three weeks .

Post cardioversion for 4 weeks. Then based on risk factors assess the risk

Most occur in < 72 hrs. Not needed in < 48 hrs. Symptoms are unreliable--- ECG documentation

needed…otherwise assume > 48 hrs..

Newer agents Why? Disadvantage of OAC Inter individual variation Drug /food interactions Regular INR check up needed--- monthly. DABIGATRAN (pradaxa)--- direct thrombin inhibitor REL –Y trial --- same as warfarin in stroke prevention Higher dose more effective but with risk of bleeding. No INR monitoring,150-220 mg daily FDA approved------- NEJM

2009 361(2);1139-51 RIVAROXABAN (xaretto)--- factor X a inhibitor Related to linezolid,mitochondrial toxicity ROCKET AF trial

Other ways

LAA occlusion Most common source of embolism WATCHMAN device PROTECT AF trial Periprocedural complications more Used when OAC contraindicated lancet

2009 ;374;534--40

RATE VS RHYTHM CONTROL

Theoretically rhythm control > rate control But complications anti arrhythmic drugs. End points RESULTS

All causes mortality no difference

CV mortality no difference

Non cardiovascular mortality

more with rhythm

stroke no difference

Quality of life no difference

Cost rhythm control less cost

Outcome

AFFIRM

better in STAF J RHYTHM trials

RHYTHM

CHOICE OF STRATEGY

FAVORS RATE CONTROL RHYTHM CONTROL

Persistent AF paroxysmal AF

Recurrent AF First episode

Less symptomatic More symptomatic

> 65 yrs < 65 yrs

HTN No HTN

No h/o CHF h/o CHF

Previous rhythm treatment failure.

Patient preference

Rate control drugs

Atrioventricluar blocking agents Calcium channel blockers Beta blockers Amiodarone Digoxin

ABCD

Rate control

Bblockers , CCBs , digoxin are effective for rate control.

Do not convert AF into NSR. C/I in pre excitation Amiodarone for both rate and rhythm control. Several side effects limits its use as first line drug.

Choice of drugs depends upon the clinical presentation

Normal systolic function:

IV CCBs non dihydropyridine group IV BBs --- class I recommendation

LVD or HF : IV digoxin or IV amiodarone –class I recommendation In case of AV nodal blocking agents C/I

DILTIAZEM: Chemical defibrillator 0.25 mg /kg (15-20 mg ) given IV over 2 minutes. Monitor HR and BP Rapid onset of action –within 10 min 0.35 mg /kg (20-25 mg )IV over 4 min HR < 100bpm ---maintenance dose 5-15 mg /hr is

infused t1/2 3-4 hrs Oral dose within 3 hrs of IV dose. 1.5 * total IV dose 120-360 mg three to four divided doses SR prepartion is useful in case of OD

VERAPAMIL: 0.075-0.15 mg /kg (5-10mg) given IV over 2 min Same if needed after 15 to 30 min T ½ -- 4-12 hrs. No need of continuous maintenance infusion More hypotensive and more negatively inotropic than

diltiazem. Hypotension responds to IV calcium gluconate 1 gm. Oral maintenance does is 120-360 mg in divided

doses.

Beta blockers

In myocardial ischemia Thyrotoxicosis Class I recommendation• Metoprolol: Selective B1 blocker 2.5 -5 mg IV over 2 min .. Up to three doses ( max 15

mg) Oral maintenance dose of 25-100mg (50 mg) bid • Atenolol– use in hypertension 5mg IV—50 mg od• Propanolol – 0.15 mg /kg -- 80 -240 mg /day• Esmolol--- 0.5mg/kg over I min 60- 200mcg /min

digoxin

Not used when LV function is preserved. In hypotension In COPD LVD Class 1 recommendation Not effective as monotherapy. Not useful in exercise and thyrotoxicosis

amiodarone

• Class II a recommendation in case of preserved LV Function

• Class II b recommendation when rate control is not achieved by other agents.

Patients with LVD

• Digoxin: 0.25 mg IV over 2 min every 2 hours. Not to exceed 1.5 mg IV over 24 hrs Maintenance dose is 0.125-0.375 mg daily IV or orally.

Orally 0.5 mg daily for 2-4 days— 0.125– 0.375 mg daily

Slow onset of action Effective in controlling heart rates at rest as well as

in individuals who are sedentary But not so in adrenergic stress,hyperthyroidism,copd?

Amiodarone: Acute setting 150 mg IV over 10 min maintenance infusion of 1 mg/ min IV over 6 hrs , 0.5 mg /min IV over 18 hrs.. Orally ,late onset of action – not in acute setting Oral dose is 800 mg /day in divided doses /week Oral maintenance dose 200mg daily. Affects the pharmacokinetics of digoxin , warfarin ,

verapamil — reduced dose

WPW SYNDROME

Use of AV nodal blocking agents is dangerous. Allows the fibrillatory waves to pass freely through

the bypass tract--- VF Type Ia agents which increase refractory period of

bypass tract –procainamide Inhibit both AV node and bypass tract– type Ic and

type III ibutilide or amiodarone IV to control ventricular rate.

Or else use EC

Non pharmacologcial control of VR in AF

In case of tachycardia induced cardiomyopathy

AV nodal ablation : if the VR in AF cannot be controlled by AV Nodal blocking agents AV nodal ablation with permanent ventricular pacemaker is an option

• Agents should be tried

Pulmonary vein isolation:• Surgically or RFA

NO STRUCTURAL HEART DISEASE DILTIAZEM, VERAPAMIL, BB

CAD, EF > 40 % BB ,CCB S

LVD EF < 40 % DIGOXIN ,BB s

REFRACTORY CASES AMIODARONE,DRONEDARONE,AV NODAL ABLATION

What is effective rate control?

At rest HR , 80 /MIN HOLTER MONITROING rest --- < 80/min no hour averaging ----- 90 / min Moderate exercise 90 – 115 /min Peak exercise 120 /min 20- 30 % REDUCTION of age predicted HR

RATE CONTROLLING DRUGS

Rhythm control

Not necessary in all patients In AFFIRM trial (Atrial Fibrillation Follow up

Investigation of Rhythm Management) RACE Rate control vs Electrical Cardioversion for

Persistent Atrial Fibrillation No change in mortality or incidence of stroke in both

groups.

Symptomatic and LVFpatients

Methods

Electrical cardioversionPharmacological cardioversion• Risk of thromboembolisation • Increased if > 48 hrs.

• Spontaneous conversion – many patients of AF• Mostly during the first 24-48 hrs.• Less as duration prolongs• Very less > 7 days• Efficacy of drugs also decrease.

Cardioversion

Electrical or pharmacological When? Which is better? In whom?

When --- symptomatic AF,newly AF,post op AF Which -------- electrical > pharmacological Whom? ------- persistent,paroxysmal

Do all need ?

Severely symptomatic ,less severe symptomatic acute AF --- to be cardioverted…..

“restoration of SR is a reasonable goal in patients who have a first time diagnosis of AF regardless of symptoms unless some indications shows that AF has been prsent for many years before identification…….” CARDIOLOGY CLINICS

In asymptomatic to slow progression of AF

Duration of paroxysmal event progression of AF Effective in short duration AF Not useful in old , asymptomatic Therapeutic anticoagulation in all.. Biphasic > monophasic Even in presence of structural heart disease.

Electrical cardioversion

Success – adequate current flow Biphasic > monophasic Deep sedation required. No effect of pad size or paddle positioning. Shock delivery not during vulnerable phase---VF In synchronized mode— R wave sensing. In defibrillation mode --- in an asynchronous

fashion. 200/360 J In emphysema,obesity,asthma---expiratory

phase

Implanted devices --- AP postioning Why?--- no effect on device. Device commanded cardioversion. In AFL –antitachycardio pacing is required,no

sedation. Internal cardioversion --- by catheters—rt

atrium,LCS,LPA.

Aftercardioversion

Persistent restoration of AF IRAF Failed cardioversion

IRAF---immediate recurrence of AF 5%-25% Triggered by APCs Pretreatment with fleicainide useful. Failed cardioversion – 10 % Amiodarone,ibutilide useful.

Positoning of paddles

RHYTHM CONTROL DRUGS

Theoretically useful Less symptoms Good effort tolerance Less hospitalisations But more compications by drug itself

Pharmacolocigal cardioversion

No IV sedation < 7 days of onset Less effective than electric Toxic effects of drugs

Type Ia agents – procainamide,quinidine,disopyramide

Type Ic agents – propafenone , fleicainide Type IIIagents -- ibutilide, dofetilide amiodarone

Hospitalised Exception is amiodarone

Type Ia and Ic convert AF –AFL BB or CCBs to be given half n hour before them.

Agents • AF< 7 days : Class I recommendation Class Ic fleicainide or propafenone Class IIa Class III dofetilide or ibutilide Class IIb – amiodarone class III --- sotalol,digoxin

Preserved systolic function

Flecainide: Class I recommendation Orally or IV 200-300 mg given once Only after effective response in hospitalisation –pill in

pocket approach to be used. IV Dose is 1.5 -3.0 mg/kg given over 10-20 min

Propafenone: Class I recommendation Oral –600mg given once IV dose 1.5-2.0 mg /kg over 10-20 min 56-83%

Ibutilide: IV only 1 mg over 10 min Dose repeated

Dofetilide: c/I in renal dysfunction 500 mcg bid 500-100 mcg daily QT interval to be monitored

Amiodarone: 5-7 mg/ kg IV over 30- 60 min 1.2 -1.8 g/day of infusion—10 gms 200-400mg/day is maintenance

Quinidine: 0.75-1.5 gm in divided doses Digitalis toxicity

In LVD

Only amiodarone and dofetilide 100-400 mg daily

>7 days: Class III agents are effective

Choice of anti arrhythmic drugs in the treatment of AF with assosciated co morbidities

Lone AF CHF CAD LVH

1st line Fleicainidepropafenone

Amiodaronedofetilide

Sotalolamiodarone

amiodarone

2nd line SotalolAmiodaroneClass Ia

Class Ia dronedarone disopyramide

avoid Fleicainidepropafenone

Fleicainidepropafenone

In brief

Short duration AF --- highly symptomatic , no structural heart disease.

Adjunctive therapy For short duration –class Ic drugs Pill in pocket approach only after intial

hospital response --- based on symptoms prsent outside,

>70 kg--- flecainide 300mg, propafenone 600mg <70 kg --- flecainide 200 mg , propafenone 450

mg Long duration 20-30 % cases

Surgical ablation: Maze procedures –atrial incisions In conjunction with other surgical operations Replacemnt of mirtal valve CABG

Pacemakers

RV placed pacemaker.. Prevents AV asynchrony Prevents reentry Prevents bradycardia induced dispersion of atrial

depolarisation.

Other drugs

Beneficial role ACEI ARBS Prevents structural remodelling. Blocks RAAS STATINS OMEGA 3 FATTY ACIDS VITAMIN C STEROIDS RANOLAZINE-RANEXA --- MERLIN AF TRIAL Na channel blocking drug..

New drugs

DRONEDARONE( multaq):sanofi aventis Amiodarone like compound Lacks iodine moiety Spans all classes K currents,INa,Ikr,Ikach,L type ca ,β blocking,prolongs AP, T ½ --24 hrs Dronedarone AF study after EC—prevention of AF 800mg

optimal dose. ANDROMEDA study– tolerability in CHF DANE trial ADONIS,EURIDIS 400mg bid

CELIVARONE: SSR 149744C Benzofuran derivative Structurally related to amiodarone Inhibits k currents 300mg or 600 mg. ATI 2001 Synthetic analogue of amiodarone More potent than amiodarone in atrial properties T1/2 –12min

Class III drugs

AZEMILIDE: 125 mg daily Neutropenia,torsades de pointes TEDISAMIL: Multiple k channels Decreases rate Increases AP in atria Antianginal drug BERTOSAMIL on clinical trials

Atrial depolarization delaying agents

• VERNAKALANT Na ,k blockers Atrial selectivity 61 % conversion 3mg/kg over 10 min --- 2 mg /kg Dysguesia,nausea,vomting• AVE 0118 Ikur,ito,ikach No QT prolongation• AZ7009• SEROTONIN type 4 antagonists• RS 100302

New drugs

Adenosine agonists CVT –510 : Slowed av conduction No negative inotropic ,vasodialtion,hypotension

effects.

Ambasilide Almokalant Sematilide Tedisamil Ximelgatran –SPORT IF trial Rotigaptide---gap junction modulator

WHAT DOES TRIALS SAY?

AFFIRM trial : RACE trial : AF –CHF trial ALL reveal no change in mortality in both groups. Treatment is individuialised

AFFIRM trial : management of AF with the rhythm control strategy offers no survival advantage over the rate control strategy.anticoagualtion to be continued in this group of high risk patients .

ATHENA trial :a trial with dronaderone to prevent hospitalisation or death in AF

400mg bid dose ANDROMEDA –european trial of dronedarone in

moderate to severe CHF---400 mg bid CAFÉ trial : canadian AF evaluation study. SAFIRE –D study –doefetilide use in AF 500ug dose. CRAFT REL-Y TRIAL 110mg -150 mg of dabigatran. RECOVER –in dvt ROCKET AF –rivaroxaban EINSTEIN ---vte ATLAS ACS –in ACS

trial Follow up

No. of subjects

AF charct

Rhythm control

Ratecontrol

1 endpoints

Summaryresults

PIAF2000

I yr 252 Persistent7d-1yr

AmioECV

Dil,BB,Dig,RFA

Sym .improve

No diffRhytm=↓FC,rate=↓h

PAF22002

1.3y 141 Paroxysmal,severe sym.

A,pro,flc,sot:ECV

RFA Dev of Per.AF

RH=↓pAFRate=↓CHF

AFFIRM2002

3.5y 4,060 Persistentparoxysm

A,S,P,AAD:ECV,non pharm

BB,D,V,dig,RFA

death No diif in end point

RACE 2002

2.3y 522 Pers(32d)recAFaftrECV

S,F,P,A:ECV

BB,D,V,dig,RFA

Composite cl.evnts

Rate nt inferior fr 1 end point

STAF 2003

1.7y 200 Persistent>4wks

A,P,F:ECV BB,D,V,dig,RFA

composite

No change

HOTCAFÉ2004

1y 205 Persistent7d-2yr

ECV-P,S,digRec-rpt,A

BB,dig,v,RFA

Composite

No difference

Ongoing trials/new trials 625 trials so far 1.Apixaban– novel factor X a inhibitor 5mg bid AVERROES study –phase III Compared with aspirin Double blinded RCT 2.efficacy of olmesartan in paroxysmal AF ANTI PAF trial –40 mg OD 3.EPLERAF study ---eplerenone in the prevention of AF

recurrence after cardioversion 4.vernakalant hcl efficacy in AF 5.WISDOM trial –withdrawal or continuation of amiodarone

in successfully treated patients with persistent AF 6.w 3 fatty acids for prevention of post OP AF--- OPERA

Recent advances

ACC/AHA 2010 guidelines How to handle rate control therapy Recently introduced antiarryhtmic drugs Catheter based treatment Antithrombotic therapy No benefit of achieving strict heart rate control <80

bpm at rest <110 bpm on exer cise ---class IIIevidence b

Dronedarone not to be used in LVD Catheter ablation –class Ia –A evidence in paroxysmal

Afnormal atria,class II b --- paroxysmal with LVD,Iia –persistent

Dabigatran –seminal event in AF management

Take home message

Most common sustained cardiac arrhythmia All three properties of arryhtmia play a role. Foci of intiation diagnosed. Treatment depends upon duration. Treatment changes on age,presence of LVD Anticoagualtion or antithrombotic based on assessment of

risk factors.. Rate control = rhytm control on long term theoretically rhythm control is better. Not useful in permanent AF. Catheter ablation is becoming the major option in treatment. Effects of antiarryhthmic drugs are overcome by new drugs. INR need not be monitored witn dagibatran

Ganong Samson and wright physiology Guyton www.emedicine.com www.aha.org www.atrialfibrillation.com

And finally I landed up in AF ---DOCTORS SYMDROME….THANK YOU for your attention

Professor: define seminar

Student :seminar is defined as process in which one spoils his sleep for one night in an effort to make others sleep.

Thank youDr.P.L.JOHN ISRAELH.O.D OF GENERAL MEDICINE

THANK YOU