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Cardioversion of Atrial Cardioversion of Atrial Fibrillation Fibrillation Clinical Issues Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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Page 1: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Cardioversion of Atrial FibrillationCardioversion of Atrial FibrillationClinical IssuesClinical Issues

Christopher Granger, MD

Director, Cardiac Care Unit

Duke University Medical Center

December 2007

Page 2: Cardioversion of Atrial Fibrillation Clinical 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

Page 3: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 4: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 5: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 6: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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%

Page 7: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 8: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 9: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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.

Page 10: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Trials of Rate vs Rhythm ControlTrials of Rate vs Rhythm Control

ACC/AHA/ESC Guidelines 2006

Page 11: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 12: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 13: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 14: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 15: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

When and Why Acutely Cardiovert?

Page 16: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 17: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Lip GY Lancet 2007;370:604-18

Page 18: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Lip GY Lancet 2007; 370:604-18

Page 19: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 20: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 21: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

How often does spontaneous conversion occur over 8 weeks?

Page 22: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 23: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Klein A et al. N Engl J Med 2001;344:1411-1420

Page 24: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 25: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 26: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 27: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 28: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 29: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007
Page 30: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

Predictors of Cardioversion with Ibutilide201 patients treated

Predictors of Cardioversion with Ibutilide201 patients treated

Zaqqa AJC 2000

Page 31: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 32: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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 (

%)

Page 33: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

How often does spontaneous conversion occur after

months of AF?

Page 34: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 35: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 36: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 37: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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

Page 38: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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.

Page 39: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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Page 41: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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Page 42: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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Page 43: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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Page 44: Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

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