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Management of Atrial Fibrillation
Dr.Ajmal Khan TMO Cardiology HMC
The Consequences of AFThromboembolism· Stroke: 4.5 increased risk· Microemboli: reduced cognitive
function· Prothrombotic state
Mortality· 2 increased risk independent
of comorbid CV disease· Sudden death in HF and HCM
Hospitalizations· Most common arrhythmia
requiring hospitalization· 2-3 increased risk for
hospitalization
Impaired Hemodynamics· Loss of atrial kick· Irregular ventricular contractions· HF· Tachycardia-induced
cardiomyopathy
Reduced QoL· Palpitations, dyspnea, fatigue,
reduced exercise tolerance• AF is an enormous contributor to the growing cost of medical care
Definition AF is a supraventricular tachyarrhythmia
characterized by uncoordinated atrial activation with consequent deterioration of mechanical function.
ECG shows, rapid oscillations, or fibrillatory waves that vary in amplitude, shape, and timing, replace consistent P waves, and there is an irregular ventricular response.
Classification
• Recurrent AF :(1) paroxysmal AF (2) persistent AF (3) permanent AF
Paroxysmal(Self-terminating)
First Detected
Permanent
Classification of Atrial FibrillationACC/AHA/ESC Guidelines
Persistent(Not self-terminating)
Epidemiology of Atrial Fibrillation• Most common sustained cardiac arrhythmia.
• 0.4% to 1% in the general population.• 8% in those older than 80 y.• Currently affects > 2.3 million Americans, or 1% of
population.
• Preferentially affects men and the elderly .• Prevalence expected to increase by ≥ 2.5-fold
by 2050 .• Lifetime risk of developing AF: 1 in 4 for men and
women ≥ 40 years of age .
Prevalence of Diagnosed AF
Go AS, et al. JAMA. 2001;285:2370-2375.
Prev
alen
ce (%
)
0
2
4
6
8
10
12
< 55 55–59 60–64 65–69 70–74 75–79 80–84 ≥ 85
Women
Age (years)
11.1
9.110.3
7.27.3
5.05.0
3.43.0
1.71.71.00.9
0.40.20.1
1.89 million adults in study population; N = 17,974 with AF
Men
Projected Number of Patients with AF by 2050
ATRIA = Anticoagulation and Risk Factors in Atrial Fibrillation.Naccarelli GV, et al. Am J Cardiol. 2009;104(11):1534-1539.
Year
2.08 2.44
5.1
5.1
0
2
4
6
8
12
14
16
1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Patie
nts
with
AF
(mill
ions
)
3.03
7.56
5.42
11.7
15.2
4.34
9.4
11.7
3.33
7.5
8.9
2.94
6.8
7.78.4
10.2
3.804.78
10.3
13.1
5.16
11.1
14.3
5.61
12.1
15.9
5.6
5.9
2.66
6.1
6.7
MarketScan and Thomson Reuters Medicare Databases, 2009Olmsted County Data, 2006(assuming a continued increase in AF incidence)
ATRIA Study Data, 2000
Olmsted County Data, 2006(assuming no further increase in AF incidence)
Etiologies and factors predisposing patients to AF
Electrophysiological abnormalities
Enhanced automaticity (focal AF) Conduction abnormality (reentry) Atrial pressure elevation
Mitral or tricuspid valve disease Myocardial disease (primary or secondary, leading to systolic or diastolic dysfunction) Semilunar valvular abnormalities (causing ventricular hypertrophy) Systemic or pulmonary hypertension (pulmonary embolism) Intracardiac tumors or thrombi Atrial ischemia
Coronary artery disease
Etiologies and factors predisposing patients to AF
Inflammatory or infiltrative atrial disease
Pericarditis Amyloidosis Myocarditis Age-induced atrial fibrotic changes Drugs
Alcohol Caffeine Endocrine disorders
Hyperthyroidism Pheochromocytoma
Etiologies and factors predisposing patients to AF
Changes in autonomic tone
Increased parasympathetic activity Increased sympathetic activity Primary or metastatic disease in or adjacent to the atrial wall
Postoperative
Cardiac, pulmonary, or esophageal Congenital heart disease
Neurogenic
Subarachnoid hemorrhage Nonhemorrhagic, major stroke Idiopathic (lone AF)
Familial AF
Diagnosis
CLINICAL FINDINGS
History • Mild symptoms : palpitations ,sweating ,fatigue.• Severe symptoms :hypotension ,myocardial
ischemia ,myocardial dysfunctions ,stroke ,mesenteric ischemia ,lower limb ischemia
• Presentations of precipitating factors • Asymptomatic
Examination
• Irregularly irregular pulse • Pulse deficit• Also look for
Hypertension ,Thyrotoxicosis ,CCF ,MS, Pulmonary diseases ,Other causative factors.
Clinical evaluation in patients with AF
Electrocardiogram, to identify• Rhythm (verify AF) • LV hypertrophy • P-wave duration and morphology or fibrillatory waves • Preexcitation • Bundle-branch block • Prior MI • Other atrial arrhythmias • To measure and follow the R-R, QRS, and QT intervals in
conjunction with antiarrhythmic drug therapy
Clinical evaluation in patients with AF
Transthoracic echocardiogram, to identify• Valvular heart disease • LA and RA size • LV size and function • Peak RV pressure (pulmonary hypertension) • LV hypertrophy • LA thrombus (low sensitivity) • Pericardial disease Blood tests of thyroid, renal, and hepatic function• For a first episode of AF, when the ventricular rate is difficult to
control
Clinical evaluation in patients with AF• Additional testing• One or several tests may be necessary. Exercise testing• If the adequacy of rate control is in question (permanent
AF) • To reproduce exercise-induced AF • To exclude ischemia before treatment of selected patients
with a type IC antiarrhythmic drug Holter monitoring or event recording• If diagnosis of the type of arrhythmia is in question • As a means of evaluating rate control Transesophageal echocardiography• To identify LA thrombus (in the LA appendage)
Management
Preventionofthrombo-embolism
ReductionofAF burden* QoL Symptoms
Reduction inthe risk ofCV eventsandhospitalizationsandcosts
Reductioninmortality
Goals of AF Management
AFib Management Treatment Options
VENTRICULARRATE CONTROL
PharmacologicNonpharmacologic
ACHIEVEMENT AND MAINTENANCE OF SINUS
RHYTHM
PharmacologicNonpharmacologic
ANTITHROMBOTIC THERAPY
Guideline-BasedAF Treatment Options
Maintenance of SR
Pharmacologic
Class IA Class ICClass III-blockers
Nonpharmacologic
Catheter ablationPacingSurgery Implantable
devices
Stroke prevention
Pharmacologic• Warfarin• Aspirin +/- clopidogrel• Dabigatran• Factor Xa inhibitorsNonpharmacologic• Removal/isolation
LA appendage
Rate control
Preventremodeling
CCBsACE-Is, ARBsStatinsFish oil
Pharmacologic• CCBs• -blockers• Digitalis• Amiodarone• DronedaroneNonpharmacologic• Ablate and pace
Rate and Rhythm ControlDefinitions
• Rate control– Rest and exertion control of ventricular response– No commitment to maintaining SR
• Rhythm control– Attempts restoration and maintenance of SR– Rate control required as needed
• Can switch from rhythm control to rate control• Difficult to switch from rate to rhythm control as
duration of AF becomes longer• ANTICOAGULATION NEEDED for either strategy
Fuster V, et al. J Am Coll Cardiol. 2006;48:854-906.
Major Trials Comparing Rhythm Strategy and Rate Strategy
• Major trials include–AFFIRM–RACE–PIAF, STAF, HOT CAFE–AF-CHF
Trial Reference Patients (n)
AF duration
Follow-up (y)
Age (mean y ±SD)
Clinical events (n)
Stroke/embolism Death
Rate Rhythm Rate Rhythm
AFFIRM (2002) 128 4060 b/NR 3.5 70±9 88/2027 93/2033 310/2027 356/2033
RACE (2002) 124 522 1 to 399 d 2.3 68±9 7/256 16/266 18/256 18/266
PIAF (2000) 130 252 7 to 360 d 1 61±10 0/125 2/127 2/125 2/127
Trials comparing rate control and rhythm control strategies in patients with AF
AFFIRM: All-Cause Mortality
Rate N:
Rhythm N:
2027
2033
1925
1932
1825
1807
1328
1316
774
780
236
255
0
5
10
15
20
25
30
0 1 2 3 4 5
Mor
talit
y, %
RateRhythm
p=0.078 unadjusted
Time (years)
p=0.068 adjusted
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
Favors Rate Control Favors Rhythm Control
Persistent AF Paroxysmal AF
Newly Detected AF
Less Symptomatic More Symptomatic
>65 years of age < 65 years of age
Hypertension No Hypertension
No History of Congestive Heart Failure Congestive Heart Failure clearly
exacerbated by AF
Previous Antiarrhythmic Drug Failure No Previous Antiarrhythmic Drug Failure
Canadian Cardiovascular Society Recommendations 2011
Cardioversion of AFib
• Pharmacological– Early onset AFib– Long-standing AFib
• Electrical
Pharmacological Cardioversion
Our Goal
Pharmacological Cardioversion• More effective in recent-onset AFib
– Class IA-IC-III drugs administered IV– Class IC favoured in non-cardiopathic patients – Class III favoured in cardiopathic patients or those
with delays in conduction• Oral loading can be performed with class IC drugs
– Flecainide (200-300 mg) – Propafenone (450-600 mg)
Treatment Out-of-Hospital with Class IC Drugs
• Symptomatic, rare episodes of AFib• Recent onset AFib• No structural heart disease• Prior hospital experience• Good physician-patient relationship• Resting conditions for at least 4 hours
Pill-in-the-Pocket
• In a selected (no or mild HD), risk-stratified patient population with recurrent AFib not currently taking AADs
– 79% developed ≥ 1 episodes of recurrent AFib during 15 ± 5m follow-up
– Acute oral flecainide or propafenone successfully terminated 94% of episodes within 113 ± 84 min, with side effects in 7% of patients
Alboni P, et al. N Engl J Med (2004) 351: 2384
Amiodarone for Cardioversion of Recent-Onset AFib: Meta-analysis
• Amiodarone IV (3-7 mg/kg ± infusion 0.9-3.0 g/day)
• Amiodarone oral (25-30 mg/kg)
• Time to conversion > 6-8 h
• Amiodarone > 1.5 g/day IV > placebo
• Amiodarone 25-30 mg/kg oral > placebo
• Amiodarone not > other AADs
• Safe in patients with structural cardiopathies and low LVEF
100
80
60
40
20
Con
vers
ion
(%
)
Bolus onlyBolus+infusion
2-4 h 8 h0
34
55
69
95
Electrical Cardioversion
Indications
• Failure of pharmacological measures for patients with AF with ongoing myocardial ischemia, symptomatic hypotension, angina, or HF.
• Immediate direct-current cardioversion is recommended for patients with AF involving preexcitation when very rapid tachycardia or hemodynamic instability occurs.
• AF of <48hr ---cardioversion without prior anticoagulation.• For high risk patients---IV UFH or LMWH before
cardioversion.• AF of > 48 hr or uncertain duration follow the protocol of
anticoagulation.
A Safety-Driven Approach
2011 ACC/AHA/HRS Guidelines:Antiarrhythmic Approaches to Maintain SR in Patients with Recurrent PAF
or Persistent AF*
HF
AmiodaroneDofetilide
Maintenance of SR
AmiodaroneDofetilide
Catheterablation
DronedaroneFlecainidePropafenoneSotalol
No (or minimal)heart disease
DronedaroneFlecainidePropafenoneSotalol
Amiodarone
No Yes
AmiodaroneDofetilide
Catheterablation
Catheterablation
HTN
Substantial LVH
CAD
Catheterablation
Amiodarone Catheterablation
DofetilideDronedroneSotalol
Efficacy of AADs in AF Trials
DronedaroneSotalol
Amiodarone
Class ICPlacebo
100
80
60
40
20
0
Patie
nts
in S
R at
1 Y
ear (
%)
CTAF SAFE-T AFFIRM DAFNE* EURIDIS* ADONISEURIDIS/ADONIS Pooled
DIONYSOS†
Treatment Options for AFib
Drugs to Control Ventricular Rate
Permanent AFib and Ventricular Rate Control
Indications for control of ventricular rate:
• Failure of antiarrhythmic therapy for preventing recurrence
• Alternative treatment to maintain sinus rhythm
Favors Rate Control Favors Rhythm Control
Persistent AF Paroxysmal AF
Newly Detected AF
Less Symptomatic More Symptomatic
>65 years of age < 65 years of age
Hypertension No Hypertension
No History of Congestive Heart Failure Congestive Heart Failure clearly
exacerbated by AF
Previous Antiarrhythmic Drug Failure No Previous Antiarrhythmic Drug Failure
Canadian Cardiovascular Society Recommendations 2011
Anticoagulation and Antiplatelet Therapy
Intermittent AFPermanent AF
Annual Stroke Rate (%)
AF and Stroke• AF increases stroke risk 4- to 5-fold
• Stroke is the most common and devastating complication of AF
– Incidence of all-cause stroke in patients with AF is 5%
• AF is an independent risk factor for stroke.
– Risk for stroke increases with age
• Stroke risk persists even in asymptomatic AF
• Stroke risk persists in patients with a “high-risk” profile despite a strategy of rhythm control (AFFIRM study, RACE study)
Low
RiskModerateRisk
HighRisk
10
8
6
4
2
0
Approach to thromboprophylaxis in patients with AF
Stroke Risk Stratification in AFCHADS2 Risk criteria score
Risk Factor Score
Cardiac failure 1
HTN 1
Age ≥75 y 1
Diabetes 1
Stroke 2
Lip GY, Halperin JL. Am J Med. 2010;123(6):484-488.
CHAD2 score and stroke rate
Less validated or weaker risk factors Moderate-risk factors High-risk factors
Female gender Age greater than or equal to 75 y
Previous stroke, TIA or embolism
Age 65 to 74 y Hypertension Mitral stenosis
Coronary artery disease Heart failure Prosthetic heart valvea
Thyrotoxicosis LV ejection fraction 35% or less
Diabetes mellitus
Risk category Recommended therapy
No risk factors Aspirin, 81 to 325 mg daily
One moderate-risk factorAspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5)
Any high-risk factor or more than 1 moderate-risk factor
Warfarin (INR 2.0 to 3.0, target 2.5)
Antithrombotic therapy for patients with atrial fibrillation
Warfarin vs Placebo inStroke Prevention in AF
100% 50% 0% -50% -100%
AFASAK-1
SPAFBAATAF
CAFA
SPINAF
EAFT
ALL Trials
Favors Warfarin Favors Placebo/Control
Hart R, et al. Ann Intern Med. 2007;146:857-867.
Warfarin reduces incidence of stroke by about 64%
ACTIVE = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events.
Antiplatelet Therapy in AFACTIVE-W:6706 randomized patients;trial stopped
6
4
0
2
Out
com
e/Ye
ar (%
)
StrokeVascularEvent
MajorBleeding
5
3
1
P = .0003
P = .001 P = .53
WarfarinClopidogrel +ASA
Active = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events. ACTIVE Investigators. N Engl J Med. 2009;360(20):2066-2078.
Antiplatelet Therapy in AFACTIVE-A:7554 randomized patients;median follow-up of 3.6 years8
6
4
0
2
Out
com
e/Ye
ar (%
)
StrokeVascularEvent
MajorBleeding
7
5
3
1
P = .01
P<.001
P<.001
ASAClopidogrel +ASA
NEW ANTICOAGULANTS
Characteristics of new oral anticoagulants
Sobieraj-Teague M, et al. Semin Thromb Hemost. 2009;35:515-524.
AgentMechanism of
ActionDosing Onset Half Life Reversibility
Clinical Development
Apixaban Direct factor Xa inhibitor
Oral2x daily
3 hr 12 hr NoPhase 3;
ARISTOTLE, AVERROES
RivaroxabanDirect factor Xa inhibitor
Oral1–2x daily
3 hr 9 hr NoPhase 3;
ROCKET AF
DU 176bDirect factor Xa inhibitor
Oral1–2x daily
1–2 hr 9–11 hr NoPhase 3;
ENGAGE-AF
BetrixabanDirect factor Xa inhibitor
Oral2x daily
Not reported
19 hr NoPhase 2;
EXPLORE Xa
YM 150Direct factor Xa inhibitor
Not reportedNot
reportedNot
reportedNo Phase 2
IdrabiotaparinuxIndirect factor Xa inhibitor
WeeklySC Injection
1–2 hr 80–130 hr Yes, IV avidinPhase 3;
BOREALIS–AF
Dabigatran etexilate
Direct thrombin inhibitor
Oral1–2x daily
1–2 hr 12–17 hr No Phase 3; RE–LY
AZD 0837Direct thrombin inhibitor
Oral1–2x daily
1 hr 9 hr No Phase 2
ATI-5923Tecarfarin
Vitamin K antagonistVariable
Oral 1x dailyNot
reported136 hr Yes, vitamin K
Phase 2/3; EMBRACE AC
Connolly S, et al. N Engl J Med. 2009;361:1139-1151.
Stroke Prevention in Atrial FibrillationDabigatran etexilate vs warfarin (RE-LY)
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
Stroke/SystemicEmbolism
Major Bleed IntracranialHemorrhage
Perc
ent/
Year
Dabigatran 110 mgDabigatran 150 mgWarfarin INR 2.0–3.0
***
†
†† §
Dabigatran vs warfarin* P < 0.001 Non-inferiority**P < 0.001 Non-inferiority, superiority†P = 0.003††P < 0.001§ P < 0.001
AVERROES TrialASA(81-324 mg daily; up to 36 mo/end of study)
Apixaban(5 mg twice daily; 2.5 mg in selected patients up to 36 mo/end of study)
E
Unsuitable for warfarin therapyN= 5600
Double-blind
AVERROES, Apixaban Versus ASA to Reduce the Risk Of Stroke.
R
Cum
ulati
ve R
isk
0.0
0.01
0.03
0.05
0 3 6 9 12 18 21
ASA
Apixaban*
No. at RiskASAApix
2791 2720 2541 2124 1541 626 3292809 2761 2567 2127 1523 617 353
Months
RR=0.4595% CI, 0.32-0.62P<.001
AVERROES: Stroke or Systemic Embolic Event
Clinical Challenges With New Anticoagulants
• No validated tests to measure anticoagulation effect• No established therapeutic range• No antidote for most agents• Assessment of compliance more difficult than with
vitamin K antagonists• Potential for unknown long-term adverse events• Balancing cost against efficacy• Lack of head-to-head studies comparing new agents
Catheter AF Ablation
Indications:• Symptomatic AF refractory or intolerant to at
least 1 class I or III AAD.• Selected symptomatic patients with HF and/or
reduced ejection fraction• Presence of an LA thrombus is contraindication
to catheter ablation of AF• Discontinuation of anticoagulation is not an
indication for ablation
A. Circumferential ablation around left and right PV antra
B. and C. Additional linear lesion sets for the roof, mitral isthmus, carinae, SVC, and cavotricuspid isthmus
D. Targeting fractionated electrograms and/or ganglionic plexi
Common Lesions Performed in AF Ablation
A. B.
LSPV
LIPV
RSPV
IVC
RIPV
LSPV
LIPV
RSPV
IVC
RIPV
LSPV
LIPV
RSPV
IVC
RIPV
SVC
C. D.
LSPV
LIPV
RSPV
IVC
RIPV
SVC
SVCSVC
Treatment of atrial fibrillation in special population
Management of atrial fibrillation associated with the Wolff-Parkinson-White (WPW) preexcitation
syndrome
Immediate direct-current cardioversion is recommended in hemodynamically unstable patients.
Intravenous procainamide , ibutilide ,flecainide or amiodarone is recommended to restore sinus rhythm in hemodynamically stable patients.
Intravenous administration of AV nodal blocking drugs i.e. digitalis glycosides or nondihydropyridine calcium channel antagonists is not recommended.
Catheter ablation of the accessory pathway is recommended in symptomatic patients.
Hyperthyroidism
Administration of a beta blocker to control the rate of ventricular response .
Alternative is nondihydropyridine calcium channel antagonist (diltiazem or verapamil).
Oral anticoagulation (INR 2.0 to 3.0) is recommended in the presence of risk factors for stroke.
Management of atrial fibrillation during pregnancy
Digoxin, a beta blocker, or nondihydropyridine calcium channel to control the rate .
Flecainide , ibutilide , quinidine or procainamide to restore sinus rhythm in hemodynamically stable patient.
Direct-current cardioversion in hemodynamically unstable patient.
Anticoagulation in the presence of risk factor for stroke.
Management of atrial fibrillation in patients with pulmonary disease
Correction of hypoxemia and acidosis . A nondihydropyridine calcium channel antagonist
(diltiazem or verapamil) to control the ventricular rate.
Direct-current cardioversion in hemodynamically unstable patient.
IV flecainide may be used to restore sinus rhythm in hemodynenicall y stable patient.
Interruption of anticoagulation for diagnostic or therapeutic procedures
Anticoagulation may be interrupted for a period of up to 1 wk for surgical or diagnostic procedures.
In high-risk patients (particularly those with prior stroke, TIA, or systemic embolism), or when a series of procedures requires interruption of oral anticoagulant therapy for longer periods, unfractionated or low-molecular-weight heparin may be administered.
Summary AF is a common disease that is increasing in prevalence For any patient with AF, decisions need to be made
regarding antithrombotic therapy, rate control, and/or rhythm control
Guidelines provide recommendations for the management of patients with AF
Anticoagulation is essential in AF patients with risk markers, regardless of any restoration of SR
New agents and procedures may provide antiarrhythmic and antithrombotic options with improved outcomes for managing AF
Thank you for your attention!