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Atrial fibrillation
• wavelets propagating in different directions
• disorganised atrial depolarisation without effective atrial contraction
• f waves 350-600 beats /min.
• ventricular response is grossly irregular at 100-160 beats /min. (in WPW >300/min or VF)
AF
• potentially serious consequences:
– embolism
– impaired cardiac output
– increased mortality
• extremely common
Arch Int Med 1998 158:1316
AF
• Annual rate of stroke at FU (mean 1.6 years) was 4.7%
• LA dimension not predictive but moderate to severe LV dysfunction (any visible dysfunction greater than mild global or focal hypokinesia) independently increased risk by odds ratio of 2.5
AF:stroke risk
• previous CVA/TIA (RR 22.5)
• diabetes (RR 1.7)
• hypertension (RR1.6)
• increasing age (RR 1.4/decade)
• CCF/IHD (RR 3.0)– one of these and annual stroke risk >4%
untreated
Atrial Fibrillation
• Analysis of 6 randomised primary prevention trials has shown a 68% reduction in annual rate of stroke (4.5%-1.4%)
• reduction in mortality of 30% in the treated group
• annual rate of bleeding was 1.3%; major haemorrhage 0.3% and associated with age, hypertension and increased intensity of anticoagulation
Arch Int Med 1994 154:1449
Meta-analysis of anticoagulant studies
• aspirin (325 mg) associated with 44% stroke rate reduction
• Warfarin about 50% more effective than aspirin for prevention of ischaemic stroke
Apirin and clopidogrel
……are they safer than warfarin in AF patients?
Connolly S. American Heart Association Scientific Sessions 2005; Nov 13-16, 2005; Dallas, TX.
Vascular events and major bleeding: ACTIVE-W final results End point Clopidogrel+
ASAWarfarin Relative
riskp
Vascular events (%/year)
5.64 3.63 1.45 0.0002
Major bleeding (%/year)
2.4 2.2 1.06 0.67
AF/intensity of anticoagulation
AF
considerable heterogeneity of patients with AF so treatment strategies will differ:
– restoration and maintenance of SR
or– control of ventricular rate and anticoagulation
Falk et al Ann Int Med 1987 106:503
AF: digoxin is not the answer
• Cardioversion may be achieved with either
• electrical shock or with antiarrhythmic drugs
• digoxin is not effective in cardioverting patients from AF to SR
Cardioversion
embolism risk 0-7%– previous embolism– prosthetic valve– mitral stenosis
AF: low risk for cardioversion
• less than 2/7 duration
• absence of thrombus on TOE
• <60 years
• no clinical risk factors
Cardioversion: high risk
• require 3/52 anticoagulation pre-cardioversion
• 4/52 after cardioversion
Management of AF
• cardioversion results in SR in 90% of cases
• SR is only maintained in 30-50% at one year
• class 1a, 1c and III agents increase likelihood of maintained SR from 30-50% to 50-70% at one year
Botker et al Br Heart J 1991; 65:337-41
Digoxin and heart-rate
Matsuda et al Cardiovasc Res 1991 25:453
AF: digoxin is not the answer
• Both beta and calcium channel blocking agents control ventricular rate in AF patients at rest and on exercise
• but the negative inotropic and chronotropic effects may be deleterious to exercise tolerance
In chronic atrial fibrillation
…..pulmonary-vein ablation restores sinus rhythm
Oral, H. et al. N Engl J Med 2006;354:934-941
Circumferential Pulmonary-Vein Ablation
Oral H et al NEJM 2006;354:934-41
Ablation and chronic AF
• 146 patients with refractory chronic AF were randomly assigned to pulmonary-vein ablation or to receive short-term therapy with amiodarone.
Oral, H. et al. N Engl J Med 2006;354:934-941
Percentages of Patients without Atrial Fibrillation and Atrial Flutter in the Absence of Antiarrhythmic-Drug Therapy
Rate or rhythm
….do we really need to restore and maintain sinus rhythm, or can we simply maintain heart rate control?
EP Show – December 2002
AFFIRM
AFFIRM
AtrialFibrillation Follow-up Investigation of Rhythm Management
Inclusion criteria
Wanted to focus on the elderly
• >65 years of age
• Patients where the atrial fibrillation itself was a risk for morbidity or mortality
• Able to tolerate at least 2 drug regimens in both treatment arms
Treatment strategies
Patients were randomized to a strategy, not a specific drug regimen
• Pharmacological therapies: allowed any drug approved by North American regulatory authorities. Drugs could be added if they were approved during the trial
• Nonpharmacological therapies: allowed designated therapies once a patient failed 2 drug therapies
EP Show – December 2002
AFFIRM
Mortality results
0
5
10
15
20
25
Cum
ula
tive m
ort
ality
(%
)
Year 1 Year 2 Year 3 Year 4 Year 5
Rhythm control Rate control
N Engl J Med 2002;347:1825-33.
EP Show – December 2002
AFFIRM
Prevalence of warfarin
Greater prevalence of warfarin use in rate-control arm
•Rate-control arm: >85% throughout the trial
•Rhythm-control arm: >70% throughout the trial
N Engl J Med 2002;347:1825-33.
EP Show – December 2002
AFFIRM
Strokes
1727During warfarin but INR <2.0
Event
4425After discontinuing warfarin
80 (7.1%)77 (5.5%)Ischemic stroke
Rhythm control
(n=2033)
Rate control
(n=2027)
N Engl J Med 2002;347:1825-33.
AF
….other issues.
Lone AF
• Under age 60
• without structural cardiac disease, hypertension, diabetes, coronary heart disease or thyrotoxicosis
• low annual risk
• manage off warfarin
AF: digoxin is not the answer
In WPW and AF digoxin enhances conduction through the accessory pathway. It may lead to VF and death and should not be used in known or suspected WPW
Paroxysmal AF
• Accounts for about 65% of all AF
• commoner in young and in men
• similar stroke rates to chronic AF
• management should probably be similar too
Atrial Fibrillation-the elderly
• Median age of patients with AF is 75
• the risk of both AF and haemorrhage increase with age
• risk of bleeding shown to be a function of intensity of anticoagulation
Atrial Fibrillation-the elderly
• Close control of INR is essential and should be maintained below 3
• the elderly with clinical profiles indicating an increased risk of bleeding should not receive warfarin and aspirin is a reasonable compromise
Over 75 years
even without additional risk factors likely to benefit from
anticoagulation; care with anticoagulant monitoring
Aspirin
• 60-75 years • no clinical risk factors• risk =2%/year• warfarin contraindicated• unreliable patient
Warfarin for…...
• AF
• risk factors for stroke
• good candidate for anticoagulation
Atrial fibrillation: conclusions
• common
• significant risk of stroke
• potential for risk reduction
• restoration of atrial systole desirable
• maintenance of sinus rhythm a challenge