ATRIAL FIBRILLATION IN THE ER MAGDI SAMI, MD,FRCP(C), FACC.
-
Upload
tamsyn-porter -
Category
Documents
-
view
216 -
download
0
Transcript of ATRIAL FIBRILLATION IN THE ER MAGDI SAMI, MD,FRCP(C), FACC.
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
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