Cardioversion of Atrial FibrillationCardioversion of Atrial FibrillationClinical IssuesClinical Issues
Christopher Granger, MD
Director, Cardiac Care Unit
Duke University Medical Center
December 2007
Cardioversion of Atrial FibrillationCardioversion of Atrial FibrillationClinical IssuesClinical Issues
When and why cardiovert?
Why not wait for spontaneous cardioversion?
When and why acutely cardiovert?
How to acutely cardiovert
Electrical
Pharmacologic
Both
AFFIRMBaseline Characteristics
AFFIRMBaseline Characteristics
Age = 69.7 ± 9.0 yrs
39% female
> 2 days of AF in 69%
CHF class > II in 9%
Symptomatic AF in 88%
Age = 69.7 ± 9.0 yrs
39% female
> 2 days of AF in 69%
CHF class > II in 9%
Symptomatic AF in 88%
Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) Trial (n=522)
Van Gelder, I. et al. N Engl J Med 2002;347:1834-1840
CV death, HF, thromboembolic complications, bleeding, pacemaker, and SAEs.
Trials of Rate vs Rhythm ControlTrials of Rate vs Rhythm Control
ACC/AHA/ESC Guidelines 2006
Implications of Trials: Guideline StatementImplications of Trials: Guideline Statement
Theoretically, rhythm control should have advantages over rate control, yet a trend toward lower mortality was observed in the rate-control arm of the AFFIRM study and did not differ in the other trials from the outcome with the rhythm control strategy. This might suggest that attempts to restore sinus rhythm with presently available antiarrhythmic drugs are obsolete. The RACE and AFFIRM trials did not address AF in younger, symptomatic patients with little underlying heart disease, in whom restoration of sinus rhythm by cardioversion antiarrhythmic drugs or non-pharmacological interventions still must be considered a useful therapeutic approach. One may conclude from these studies that rate control is a reasonable strategy in elderly patients with minimal symptoms related to AF. An effective method for maintaining sinus rhythm with fewer side effects would address a presently unmet need.
Theoretically, rhythm control should have advantages over rate control, yet a trend toward lower mortality was observed in the rate-control arm of the AFFIRM study and did not differ in the other trials from the outcome with the rhythm control strategy. This might suggest that attempts to restore sinus rhythm with presently available antiarrhythmic drugs are obsolete. The RACE and AFFIRM trials did not address AF in younger, symptomatic patients with little underlying heart disease, in whom restoration of sinus rhythm by cardioversion antiarrhythmic drugs or non-pharmacological interventions still must be considered a useful therapeutic approach. One may conclude from these studies that rate control is a reasonable strategy in elderly patients with minimal symptoms related to AF. An effective method for maintaining sinus rhythm with fewer side effects would address a presently unmet need.
ACC/AHA/ESC Guidelines 2006
www.cardiosource.com
8.5
4.9
0
2
4
6
8
10
8.5
4.9
0
2
4
6
8
10
Results• No difference in primary endpoint of CV death
between groups (Figure)• Cardioversion 39% vs 8%• Also no difference in total mortality (31.8% vs.
32.9%, p = 0.73), stroke (2.6% vs. 3.6%, p = 0.32), worsening heart failure (27.6% vs. 30.8%, p = 0.17), or composite (42.7% vs. 45.8%, p = 0.20)
• Higher hospitalization rates (46% vs 39% p=.006) and cost with rhythm control
• Bradyarrhythmias ↑ in rhythm control group
Conclusions• Among patients with heart failure and atrial
fibrillation, use of rhythm control was not associated with differences in CV mortality compared with rate control
• Results were similar to AFFIRM trial, which also showed no impact on mortality with rhythm control vs. rate control for management of atrial fibrillation
26.725.2
0
10
20
3026.7
25.2
0
10
20
30
AF-CHFAF-CHF%
Trial Design: AF-CHF was a randomized trial of rhythm control (n = 682) vs. rate control (n = 694) in patients with heart failure and atrial fibrillation. Rhythm control included use of electrical cardioversion combined with antiarrhythmic drugs, including amiodarone as first-line therapy. Primary endpoint was CV death, with mean follow-up of 3 years.
Rhythm Control
Rate Control
CV Death(HR 1.06, p = 0.59)
Bradyarrhythmia(p = 0.007)
Presented at AHA Roy 2007
When and Why Acutely Cardiovert?
AF Begets AFAF Begets AF
AF causes changes in atrial electrophysiology that promote AF maintenance
AF causes changes in atrial electrophysiology that promote AF maintenance
Wijffels Circulation 1995; 92: 1954-68Wijffels Circulation 1995; 92: 1954-68
Lip GY Lancet 2007;370:604-18
Lip GY Lancet 2007; 370:604-18
Paroxysmal AF <48 hours (n=100)Paroxysmal AF <48 hours (n=100)Amiodarone IV (3 gm) vs IV Amiodarone IV (3 gm) vs IV placeboplacebo
Cotter EHJ 1999; 20:1833-42
Paroxysmal AF <1 week (n=100)Paroxysmal AF <1 week (n=100)Amiodarone IV (1.2 gm) vs placeboAmiodarone IV (1.2 gm) vs placebo
Galve JACC 1996;27:1079-82
30/50 (60%) placebo patients converted
32/50 (64%) placebo patients converted
High Rates of Spontaneous Cardioversion for High Rates of Spontaneous Cardioversion for Recent-onset AFRecent-onset AF
Likelihood of Spontaneous Conversion of Atrial Fibrillation to Sinus Rhythm
Likelihood of Spontaneous Conversion of Atrial Fibrillation to Sinus Rhythm
Danias J Am Coll Cardiol. 1998;31:588-92 Danias J Am Coll Cardiol. 1998;31:588-92
• 356 pts with AF < 72 h• Symptoms of < 24 h was only independent predictor of
spontaneous conversion (OR: 1.8, p < 0.0001)
• 356 pts with AF < 72 h• Symptoms of < 24 h was only independent predictor of
spontaneous conversion (OR: 1.8, p < 0.0001)
< 24 h
24 - 72 h
Total
< 24 h
24 - 72 h
Total
292
64
356
292
64
356
73%
45%
68%
73%
45%
68%
AF durationAF duration nn ConversionConversion
How often does spontaneous conversion occur over 8 weeks?
Klein A et al. N Engl J Med 2001;344:1411-1420
Klein A et al. N Engl J Med 2001;344:1411-1420
Clinical Outcomes at 8 Weeks among Patients with Atrial Fibrillation of More Than 2 Days Duration
Spontaneous Conversion of Patients with AF Scheduled for Electrical Cardioversion
An ACUTE Trial Ancillary Study
Spontaneous Conversion of Patients with AF Scheduled for Electrical Cardioversion
An ACUTE Trial Ancillary Study
Tejan-Sie J Am Coll Cardiol 2007;42:1638-1643
Conversion According to Duration of Pre-existing AF
Daily Conversion According to Strategy
Spontaneous Conversion of Patients with AF Scheduled for Electrical Cardioversion
An ACUTE Trial Ancillary Study
Spontaneous Conversion of Patients with AF Scheduled for Electrical Cardioversion
An ACUTE Trial Ancillary Study
Tejan-Sie J Am Coll Cardiol 2007;42:1638-1643
Multivariable Model Predicting Spontaneous Conversion
Conversion of Recent-Onset AF to Sinus Rhythm: Effects of Different Drug Protocols
Conversion of Recent-Onset AF to Sinus Rhythm: Effects of Different Drug Protocols
Mean conversion time:• Flecainide: 2.6 hrs• Propafenone: 3.0 hrs
Mean conversion time:• Flecainide: 2.6 hrs• Propafenone: 3.0 hrs
Conversion rates to sinus rhythm (%)Conversion rates to sinus rhythm (%)
* p < 0.05 vs placebo** p < 0.01 vs placebo* p < 0.05 vs placebo** p < 0.01 vs placebo
Boriani Pacing Clin Electrophysiol. 1998;21(11 Pt 2):2470-4
0
20
40
60
80
100
≤1 hr ≤3hr ≤8hr
PlaceboIV AmioIV PropPO PropPO Flec
*
**
417 hospitalized pts with AF onset ≤ 7 days417 hospitalized pts with AF onset ≤ 7 days
Cardioversion of atrial flutter and fibrillation after ibutilide infusion
(67 y/o, 15 days duration, half with prior episode)
Stambler Circulation. 1996;94:1613-1621
Predictors of Cardioversion with Ibutilide201 patients treated
Predictors of Cardioversion with Ibutilide201 patients treated
Zaqqa AJC 2000
Saliba J Am Coll Cardiol 1999;34:2031-34
Biphasic shock Refractory to standard cardioversion
(failed 2 attempts) >3 month in 55% SR in 46 (84%) of the 55 pts
Oral NEJM 1999;340:1849-54
100 consecutive patients 50 assigned conventional DC 50 pretreated with 1 mg
ibutilide
100 consecutive patients 50 assigned conventional DC 50 pretreated with 1 mg
ibutilide
0
20
40
60
80
100
No ibutilide Ibutilide
Car
diov
ersi
on s
ucce
ss (
%)
How often does spontaneous conversion occur after
months of AF?
AF 7 to 360 days duration (110 average)
CHF, recent MI, bradycardia excluded
AF 7 to 360 days duration (110 average)
CHF, recent MI, bradycardia excluded
Lancet. 2000;356:1789-94
Rhythm or rate control in atrial fibrillation:Pharmacological Intervention in Atrial
Fibrillation (PIAF) Trial
Rhythm or rate control in atrial fibrillation:Pharmacological Intervention in Atrial
Fibrillation (PIAF) Trial
Lancet. 2000;356:1789-94
Amiodarone group: 23% converted during amio load 76% had electrical cardioversion
Primary outcome: no difference
665 patients, 68 y/o
Persistent AF, 76% < 1yr
On warfarin
665 patients, 68 y/o
Persistent AF, 76% < 1yr
On warfarin
0.8
27.124.2
0
5
10
15
20
25
30
placebo amio sotalol
Spontaneous Conversion 28 DaysSpontaneous Conversion 28 Days N Engl J Med 2005;352:1861-72
Electrical
More effective (90%)
Quick
One procedure with TEE
Cardioversion itself safe
Electrical
More effective (90%)
Quick
One procedure with TEE
Cardioversion itself safe
Pharmacological
Works well for recent onset, for atrial flutter
Avoid sedation
Less expensive
Early maintenance enhanced by some drugs
Advantages and DisadvantagesAdvantages and Disadvantages
What do the Guidelines Say?
Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Circulation. 2006;114:e257-e354.
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Cardioversion of Atrial FibrillationCardioversion of Atrial FibrillationClinical IssuesClinical Issues
Cardioversion is common practice, albeit not well supported in trials that have been done
Most new onset, and many paroxysmal atrial fibrillation episodes, are treated with cardioversion if they do not spontaneously convert in 24 to 48 hours
While electrical cardioversion generally preferred, acute pharmacologic cardioversion has a role, that is not well defined