ATRIAL FIBRILLATION IN ATRIAL FIBRILLATION IN THE ERTHE ER

MAGDI SAMI, MD,FRCP(C), MAGDI SAMI, MD,FRCP(C), FACCFACC

OBJECTIVESOBJECTIVES

DIAGNOSIS OF DIFFERENT TYPES OF DIAGNOSIS OF DIFFERENT TYPES OF AF AND DIFFERENTIATE FROM OTHER AF AND DIFFERENTIATE FROM OTHER ARRHYTHMIASARRHYTHMIAS

ACUTE AND LONG-TERM ACUTE AND LONG-TERM MANAGEMENT OF AF:MANAGEMENT OF AF:WHEN TO CARDIOVERT?WHEN TO CARDIOVERT?

ELECTRIC VS CHEMICALELECTRIC VS CHEMICALWHEN TO GO FOR RATE-CONTROL?WHEN TO GO FOR RATE-CONTROL?

ACUTE & LONG-TERMACUTE & LONG-TERM

CASE 1CASE 1

Mr. J.V. 60 y old.Mr. J.V. 60 y old.

-Nov.98: first presentation with PAF at -Nov.98: first presentation with PAF at age 56. no previous cardiac history age 56. no previous cardiac history except rec. palpitation, no known CRF.except rec. palpitation, no known CRF.

-Physical exam: normal-Physical exam: normal

-ECG (show)-ECG (show)- Echocardiogram: normalEchocardiogram: normal- Lab: SMA normal, high cholesterol Lab: SMA normal, high cholesterol

What next?What next?

Methods to Restore Sinus RhythmMethods to Restore Sinus Rhythm

A. Spontaneous cardioversionB. Electrical cardioversion

1. Transthoracic2. Internal

a. intracardiacb. transesophagealc. epicardial

C. Pharmacological cardioversion1. Class 1A or 1C

2. Class III

Pharmacological ConversionPharmacological Conversion

Class 1Class 1AA (quinidine, procainamide, disopyramide)(quinidine, procainamide, disopyramide)

Class 1Class 1CC (propafenone, flecainide)(propafenone, flecainide)

Class IIIClass III (amiodarone, sotalol, ibutilide, dofetilide)(amiodarone, sotalol, ibutilide, dofetilide)

OthersOthers Digoxin, beta-blockers, calcium blockers not Digoxin, beta-blockers, calcium blockers not effective (verapamil may prevent AF recurrences effective (verapamil may prevent AF recurrences

after cardioversion)after cardioversion)

IbutlideIbutlide

• Unique iv antiarrhythmic drugUnique iv antiarrhythmic drug

• Classified as Class III according to Vaughan Classified as Class III according to Vaughan Williams ClassificationWilliams Classification

• Little effect on conduction in normal cardiac Little effect on conduction in normal cardiac

tissuetissue

Ibutilide Electrophysiologic EffectsIbutilide Electrophysiologic Effects

• No clinically significant effect on QRSNo clinically significant effect on QRS

• Produces a dose related prolongation of the QT Produces a dose related prolongation of the QT

intervalinterval

• Prolongation of QT interval is similar in men and Prolongation of QT interval is similar in men and

womenwomen

• Prolongs action potential duration and effective Prolongs action potential duration and effective

refractory periods in both atria and ventriclesrefractory periods in both atria and ventricles

Ibutilide Electrophysiologic EffectsIbutilide Electrophysiologic Effects

• Lengthens effective refractory period in both Lengthens effective refractory period in both

atrium and ventricleatrium and ventricle

• Enhances slow NaEnhances slow Na++ inward plateau current inward plateau current

and blocks delayed-rectifier outward Kand blocks delayed-rectifier outward K+ +

currentcurrent

• Maintains Class III effects even at rapid heart Maintains Class III effects even at rapid heart

ratesrates

Ibutilide Mechanism of ActionIbutilide Mechanism of Action

Na

V Max+

- APDAction Potential Duration

QRST

QT

N

Repolarization

Slow Na

(Ibutilide)

K+

Ca

plateau(other Class III)

Ibutilide Hemodynamic EffectsIbutilide Hemodynamic Effects

• No clinically significant effects on cardiac No clinically significant effects on cardiac

output, mean pulmonary arterial pressure or output, mean pulmonary arterial pressure or

capillary wedge pressure in patients with capillary wedge pressure in patients with

ejection fractions > 35 or < 35%ejection fractions > 35 or < 35%

Ibutilide PharmacokineticsIbutilide Pharmacokinetics

• Similar in all patients regardless of AF or Similar in all patients regardless of AF or

AFL, age, sex, ejection fraction, occurrence AFL, age, sex, ejection fraction, occurrence

of polymorphic ventricular tachycardia or the of polymorphic ventricular tachycardia or the

concomitant use of digoxin, calcium blockers concomitant use of digoxin, calcium blockers

or beta blockers.or beta blockers.

Ibutilide PharmacokineticsIbutilide Pharmacokinetics

• Pharmacokinetics is highly variable among Pharmacokinetics is highly variable among subjects but linear to dose of 0.01 mg/kg – subjects but linear to dose of 0.01 mg/kg – 0.1 mg/kg (0.6 – 6 mg)0.1 mg/kg (0.6 – 6 mg)

• Initial distribution half-life is 1.5 min. and Initial distribution half-life is 1.5 min. and elimination half-life averages 6 helimination half-life averages 6 h

• Clearance is primarily hepatic metabolismClearance is primarily hepatic metabolism

Ibutilide PharmacokineticsIbutilide Pharmacokinetics

• Moderate protein binding Moderate protein binding (40%)(40%)

• 8 metabolites – none of which contribute to 8 metabolites – none of which contribute to

its pharmacological effectsits pharmacological effects

• 82% of dose excreted in urine82% of dose excreted in urine

• 19 % in faeces19 % in faeces

Ibutilide Indications and Clinical UseIbutilide Indications and Clinical Use

• Ibutilide (CORVERTIbutilide (CORVERT®®) is indicated for the ) is indicated for the

rapid conversion of atrial fibrillation or atrial rapid conversion of atrial fibrillation or atrial

flutter to sinus rhythm. CORVERTflutter to sinus rhythm. CORVERT™™ should should

be considered an alternative to electric be considered an alternative to electric

cardioversion.cardioversion.

CORVERT product monograph

Ibutilide Arrhythmia Conversion: Repeat Dose Ibutilide Arrhythmia Conversion: Repeat Dose StudyStudy

2

63

2

31

0

20

40

60

80

100

Succ

ess

Rat

e (%

)

Flutter Fibrillation

Placebo

Ibutilide

Stambler B.S. et al. Circulation 1996; 94:1613

Arrhythmia Conversion: Ibutilide vs. Arrhythmia Conversion: Ibutilide vs. ProcainamideProcainamide

12

76

20

51

0

10

20

30

40

50

60

70

80

Succ

ess

Rat

e (%

)

Flutter Fibrillation

Procainamide (1200 mg)

Ibutilide (2 mg)

Volgman A.S. et al. J. Am..Coll. Card 1998: 31: 1414

Ibutilide Predictors of Arrhthmia Ibutilide Predictors of Arrhthmia TerminationTermination

0

10

20

30

40

50

60

70

Succ

ess

Rat

e (%

)

AFI AFIB

<7 Days

>7 Days

*P< 0.05

*

Stambler BS. et al. Circulation 1996; 94:1613

Ibutilide ProarrythmiaIbutilide Proarrythmia

Patients with Patients with AFIBAFIB

N/N (%)N/N (%)

Patients with Patients with AFLAFL

N/N (%)N/N (%)

All ProarrhythmiasAll Proarrhythmias 14/340 (4.1%)14/340 (4.1%) 35/218 (16%)35/218 (16%)

Non Sustained PVTNon Sustained PVT 9/340 (2.7%)9/340 (2.7%) 24/218 (11%)24/218 (11%)

Sustained PVTSustained PVT 4/340 (1.2%)4/340 (1.2%) 7/218 (3.2%)7/218 (3.2%)

% and number of patients with proarrhythmias possibly causally related to ibutlide in three placebo controlled trialsCORVERT product monograph

Polymorphic VT Risk Assessment:Polymorphic VT Risk Assessment:Independent Predictors of RiskIndependent Predictors of Risk

•Female gender

- 13.2% vs. 3.8% (P = 0.0046)

•History of heart failure -11.4% vs. 3.6% (P = 0.0305)

•Slower heart rate -78 ± 18 vs. 95 ± 26 bpm (P = 0.0348)

•Nonwhite race-15.9% vs. 3.6% (P = 0.0383)

Stambler BS. et al. Circulation 1996; 94:1613

Ibutilide Ibutilide DosingDosing

Patient Patient WeightWeight DoseDose Second iv Second iv

InfusionInfusion

60 kg60 kg

iv infusion over 10 iv infusion over 10 min.min.

1.0 mg1.0 mg

(one 10 ml. Vial)(one 10 ml. Vial)

If arrhythmia does not If arrhythmia does not

terminate within 10 min. terminate within 10 min.

after the end of the after the end of the

initial infusion, a second initial infusion, a second

10 min. infusion of equal 10 min. infusion of equal

strength maybe given.strength maybe given.< < 60 kg60 kg

iv infusion over 10 iv infusion over 10 min.min.

0.01 mg/kg0.01 mg/kg

( 0.1 ml/kg)( 0.1 ml/kg)

CORVERT product monograph

Ibutilide SummaryIbutilide Summary

Conversion efficacyConversion efficacy- AFL 60 – 80%, AF 30 – 50%- AFL 60 – 80%, AF 30 – 50%

- AF - AF arrhythmia duration (46% AF < 7 days vs. 18% AF arrhythmia duration (46% AF < 7 days vs. 18% AF 7 days) 7 days)

Superior to iv procainamideSuperior to iv procainamide Mean time to termination Mean time to termination < < 30 min30 min.. Lowers atrial DFT, prolongs ARPLowers atrial DFT, prolongs ARP Enhances efficacy of rapid pacing termination of Enhances efficacy of rapid pacing termination of

AFLAFL Proarrhythmia risk (torsade de pointes)Proarrhythmia risk (torsade de pointes)

˜̃ 2% sustained, 3% non-sustained 2% sustained, 3% non-sustained

Ibutilide Electrical vs. Pharmacological Ibutilide Electrical vs. Pharmacological ConversionConversion

Cardioversion Candidate

Atrial Flutter Atrial Fibrillation

Duration < 7d

Contraindication *to Ibutilide?

DC Cardioversion

iv Ibutilide

YES

YES YES

YES

NO

NO

K + < 4.0mEq/L

HR < 60 bpm

QTc > 440ms

Receiving Class I or III AAD

Hx torsade de pointes or polymorphic VT

Acute MI, unstable angina

Renal failure

Hepatic failure

Pregnancy or breast feeding

SHP < 90 mmHg

Age < 18 years

ECG monitoring 4h post infusion unavailable

*

CASE 2CASE 2

DF 66 Y OLD M HYPERTENSIVE DF 66 Y OLD M HYPERTENSIVE DIABETICDIABETIC

3 DAYS HISTORY OF FEELING SHORT 3 DAYS HISTORY OF FEELING SHORT OF BREATH AND PALPITATIONS OF BREATH AND PALPITATIONS

WAS RELUCTANT TO COME TO ER, WAS RELUCTANT TO COME TO ER, WAITED TO SEE HIS GP WHO WAITED TO SEE HIS GP WHO IMMETIATELY REFERRED HIM TO ERIMMETIATELY REFERRED HIM TO ER

INITIAL EXAM SHOWS FAST IRREG. HR, INITIAL EXAM SHOWS FAST IRREG. HR, BP 188/90, JVD 10 cm, BILAT. BASAL BP 188/90, JVD 10 cm, BILAT. BASAL CREPS. CREPS.

MANAGEMENT QUESTIONSMANAGEMENT QUESTIONS

CV OR RATE CONTROL?CV OR RATE CONTROL? IF CV WHAT TEST TO YOU NEED FIRST?IF CV WHAT TEST TO YOU NEED FIRST? IS CHEMICAL CARDIOVERSION SAFER IS CHEMICAL CARDIOVERSION SAFER

THAN ELECTRIC?THAN ELECTRIC? IF RATE CONTROL IS CHOSEN HOW TO IF RATE CONTROL IS CHOSEN HOW TO

PROCEED?PROCEED?AFTER THE ACUTE TREATMENT WHAT AFTER THE ACUTE TREATMENT WHAT

NEXT?NEXT?

WHAT IF THE PATIENT HAD WHAT IF THE PATIENT HAD PRESENTED WITH A PRESENTED WITH A

REGULAR TACHYCARDIA?REGULAR TACHYCARDIA?

SEE NEXT SLIDESEE NEXT SLIDE

HOW WOULD YOU TREAT THE HOW WOULD YOU TREAT THE PATIENT NOW?PATIENT NOW?

CASE 3CASE 3

24 Y OLD PREGNANT F 33 WKS24 Y OLD PREGNANT F 33 WKSPRESENTING WITH SEVERE PRESENTING WITH SEVERE

PALPITATIONS AND CHEST PAINPALPITATIONS AND CHEST PAINHER ARRHYTHMIA STARTED FOR THE HER ARRHYTHMIA STARTED FOR THE

FIRST TIME SHORTLY AFTER HER FIRST TIME SHORTLY AFTER HER SECOND CUP OF COFFEE AND HAS SECOND CUP OF COFFEE AND HAS BEEN GOING ON FOR ONE HOUR.BEEN GOING ON FOR ONE HOUR.

HOW WOULD YOU TREAT THIS HOW WOULD YOU TREAT THIS PATIENT?PATIENT?

CASE 4CASE 4

64 Y OLD HYPERTENSIVE F WHO WAS 64 Y OLD HYPERTENSIVE F WHO WAS TAKING SOTALOL 80 mg BID FOR PAFTAKING SOTALOL 80 mg BID FOR PAF

SHE RECENTLY VISITED HER GP WHO SHE RECENTLY VISITED HER GP WHO FOUND HER BP TO BE 160/90FOUND HER BP TO BE 160/90

GP STARTED HER ON 25 MG OF HCTZ GP STARTED HER ON 25 MG OF HCTZ QDQD

SINCE THEN PATIENT HAS HAD SINCE THEN PATIENT HAS HAD RECURRENT SYNCOPES AND RECURRENT SYNCOPES AND PRESENTED TO ER PRESENTED TO ER

Magdi Sami

CASE 4

Recommendations for Management of Atrial Recommendations for Management of Atrial Fibrillation < 48 HoursFibrillation < 48 Hours

Adapted from Golzari H. Ann Intern Med. 1996;125:311-323.Adapted from Golzari H. Ann Intern Med. 1996;125:311-323.

Prompt electrical or pharmacologic

conversion

Control ventricular rateConsider antithrombotic therapy

Observe for spontaneous conversion

Antiarrhythmic therapyif

No antiarrhythmic therapyif

Unstable hemodynamics or increased LA size

Stable hemodynamics, or first episode, n LA

Adapted from Golzari H. Ann Intern Med. 1996;125:311-323.Adapted from Golzari H. Ann Intern Med. 1996;125:311-323.

Recommendations for Management of Atrial Recommendations for Management of Atrial Fibrillation > 48 HoursFibrillation > 48 Hours

Control ventricular rateStart antithrombotic therapy

(heparin and/or warfarin or aspirin)

Duration < 1 year Duration > 1 year

Warfarin therapy 3-4 weeks

Cardioversion or pharmacologic conversion

Antiarrhythmic therapyif

No antiarrhythmic therapyif

Unstable hemodynamics or increased LA size

Stable hemodynamics, or first episode, n LA

Continue warfarin 1-2 monthsMonitor for recurrences

Chronic antithrombotic therapy

Assure control of ventricular rate

or