Transcript Managing Atrial Fibrillation - Scioto County Medical Society

Management of Atrial Fibrillation in 2010
John D. Hummel, MD
Ohio State University Medical Center
Ross Heart Hospital
Columbus, Ohio
Learning Objectives
• Understand the risk factors for atrial
fibrillation.
• Understand the guidelines for
anticoagulation and where there is
latitude for physician decision making.
• Be able to determine when patients
should be evaluated for curative
ablation.
Projected Number of Adults With
AF in the US: 1995 to 2050.
Adults with AF, MM
6
5
4.78
5.16
5.42 5.61
4.34
4
3.80
3
2
2.08
2.26
2.44
2.66
2.94
3.33
1
Year
Go A, et al. JAMA. 2001;285:2370-2375.
20
60
20
50
20
45
20
40
20
35
20
30
20
25
20
20
20
15
20
10
20
05
20
00
19
95
0
Atrial Fibrillation:
Costs to the Health Care System
ALOT!!
35% of arrhythmia hospitalizations
Average hospital stay = 5 days
Mean cost of hospitalization = $18,800
Does not include:
Costs of outpatient cardioversions
Costs of drugs/side effects/monitoring
Costs of AF-induced strokes
Estimated US cost burden 15.7 billion
Classification of Atrial Fibrillation
ACC/AHA/ESC Guidelines
First
Detected
Paroxysmal
(Self-terminating)
Persistent
(Not self-terminating)
Permanent
DIAGNOSTIC WORKUP
Identify Causes and Risk Factors
•
•
•
•
•
•
•
•
•
•
Minimum Evaluation
History and physical – BP, CV dz
Electrocardiogram – WPW, LVH, MI
Echocardiogram – LVH, LAE, EF, Valve Dz
Labs – TSH, Renal fxn, LFTs (Clearance,ETOH)
[D-dimer, ESR]
Additional Testing
ETT – CAD, Exercise induced SVT / AF
Holter / Event Monitor – Confirm AF and Sxs
TEE – LA clot [CXR]
EPS – SVT triggered AF
AHA / ACC / ECS Guidelines 2006
Incidence of AF Based on Presence or Absence of OSA
20 –
15 –
OSA
Cumulative
10 –
Frequency
of AF (%)
5–
No OSA
0–
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Years
Number at Risk
OSA
No OSA
844
709
569
478
397
333
273
214
173
134
110
94
70
46
29
8
2,209
1,902
1,616
1,317
1,037
848
641
502
393
296
217
195
130
94
69
28
Cumulative frequency curves for incident atrial fibrillation (AF) for subjects < 65 years of age with and without obstructive sleep apnea (OSA)
during an average 4.7 years of follow-up. p = 0.002
Gami, et al. JACC 2007;49:565-71
Goals of Therapy
1. Relieve symptoms
2. Prevent Stroke
3. Prevent Heart Failure
AF: TREATMENT OPTIONS
Rate control
Pharmacologic
• Ca2+ blockers
• -blockers
• Digitalis
• Amiodarone
Nonpharmacologic
• Ablate and pace
Prevent remodeling
Maintenance of SR
Pharmacologic
Class IA
Class IC
Class III
-blocker
ACE-I
ARB
Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D.
Stroke prevention
Nonpharmacologic Pharmacologic
• Warfarin
• Thrombin inhibitor
• Heparin
• Aspirin
Catheter ablation
Surgery (MAZE)
Nonpharmacologic
Pacing
• Removal / isolation
LA appendage
Risk Factors for Thromboembolism in AF
High-Risk Factors
Previous CVA / TIA / Embolism
Mitral Stenosis
Prosthetic heart valve
Moderate-Risk Factors
Age > 75 yrs
HTN
CHF
DM
EF < 35%
Weaker-Risk Factors
Female
CAD
Thyrotoxicosis
Age 65 – 74 yrs
AHA / ACC / ECS Guidelines 2006
Recommended Therapy
High-risk factor or > 2
moderate-risk factors
Coumadin INR 2-3
(mechanical valve INR > 2.5)
1 moderate-risk factor
ASA or Coumadin
No risk factors
ASA 81-325mg daily
D-Dimer Prediction of Risk
Evaluate whether elevated D-dimer levels can predict thromboembolic and cardiovascular events
in patients with atrial fibrillation during oral anticoagulant therapy.
Single-center, prospective, study of 269 pts with atrial fibrillation treated with warfarin
D-dimer levels were measured
End points were thromboembolic events and combined cardiovascular events (thromboembolic
events, cerebral hemorrhage, myocardial infarction, cardiovascular death).
RESULTS:
D-dimer levels were elevated (> or =0.5 microg/ml) in 63 (23%) patients.
During an average follow-up period of 756 +/- 221 days:
1.
10 (1.8%/year) thromboembolic events (8 ischemic strokes, 1 transient ischemic attack,
and 1 peripheral embolism
2.
27 (4.8%/year) combined cardiovascular events (10 thromboembolisms, 9 deaths from
heart failure, 3 sudden deaths, 2 myocardial infarctions, and 3 cerebral hemorrhages)
Patients with elevated D-dimer levels experienced higher thromboembolic and combined
cardiovascular events.
Sadanaga T, et. AL;
J Am Coll Cardiol. 2010 May 18;55(20):2225-3.
Dabigatran vs. Warfarin
Noninferiority trial randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive:
1. Fixed doses of dabigatran — 110 mg or 150 mg twice daily in a blinded fashion
2. Adjusted-dose warfarin in an unblinded fashion
The median duration of the follow-up period was 2.0 years.
The primary outcome was stroke or systemic embolism.
Results
Primary outcome
1.69% per year in the warfarin group
1.53% per year in the group that received 110 mg of dabigatran (P<0.001 for noninferiority)
1.11% per year in the group that received 150 mg of dabigatran ( P<0.001 for superiority)
Major bleeding
3.36% per year in the warfarin group
2.71% per year in the group receiving 110 mg of dabigatran (P=0.003)
3.11% per year in the group receiving 150 mg of dabigatran (P=0.31).
Hemorrhagic stroke
0.38% per year in the warfarin group
0.12% per year with 110 mg of dabigatran (P<0.001)
0.10% per year with 150 mg of dabigatran (P<0.001).
Mortality rate
4.13% per year in the warfarin group
3.75% per year with 110 mg of dabigatran (P=0.13)
3.64% per year with 150 mg of dabigatran (P=0.051).
Conclusions
Dabigatran 110 mg had rates of stroke and systemic embolism similar to warfarin with less major hemorrhage.
Dabigatran 150 mg had lower rates of stroke and systemic embolism but similar rates of major hemorrhage.
Stuart J. Connolly and the RE-LY Steering Committee and Investigators NEJM Sept 17, 2009, No. 12, Vol 361: 1139-1151
AF THERAPY
ANTITHROMBOTIC RX
AND
RHYTHM
CONTROL
OR ?
RATE
CONTROL
AFFIRM Trial: Rate vs Rhythm Control
Management Strategy Trial
• Design
– 5-year, randomized, parallel-group study
comparing rate control vs. AARx attempt at NSR
– Primary endpoint: overall mortality
• Patient population
–
–
–
–
–
–
–
4060 patients with AF and risk factors for stroke
Minimal symptoms
Mean Age = 69 yo
Hx of hypertension: 70.8%
CAD: 38.2%
Enlarged LA: 64.7%
Depressed EF: 26.0%
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
AFFIRM: All-Cause Mortality
30
Rate
Rhythm
25
Mortality, %
20
p=0.078 unadjusted
15
p=0.068 adjusted
10
5
0
0
1
2
3
Rhythm N:
2033
1932
Time (years)
1807
1316
Rate N:
2027
1925
1825
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
1328
4
5
780
255
774
236
AFFIRM: Adverse Events
Rate
Rhythm
Ischemic stroke
77 (5.5%)*
80 (7.1%)*
INR < 2.0
27 (35%)
17 (21%)
Not taking
warfarin
25 (32%)
44 (55%)
* p=0.79
The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
Time to first recurrence of AF. Time 0 is the day of randomization
100 –
Rate Control
80 –
Rhythm Control
Percent
With AF
Recurrence
60 –
40 –
Log rank statistic = 58.62
p < 0.0001
20 –
0–
0
1
2
3
4
5
6
Time (years)
N, Events (%)
Rate control:
563, 3 (0)
167, 383 (69)
98, 440 (80)
42, 472 (87)
10, 481 (92)
2, 484 (95)
Rhythm control:
729, 2 (0)
344, 356 (50)
250, 422 (60)
143, 470 (69)
73, 494 (75)
18, 503 (79)
Raitt, et al. Am H J 2006
Implications
• AFFIRM has demonstrated that rate control is
an acceptable primary therapy in a selected
high-risk subgroup of AF patients with minimal
symptoms
• Continuous anticoagulation seems warranted
in all patients with risk factors for stroke
– Asymptomatic recurrences
RACE II
•
Hypothesis: Lenient rate control is not inferior to strict rate control for
preventing cardiovascular morbidity and mortality in pts with permanent AFib
•
Randomly assigned 614 patients with permanent AF to:
–
–
•
•
•
•
•
•
lenient rate-control strategy (resting heart rate <110 beats per minute)
strict rate-control strategy (resting heart rate <80 beats per minute and heart rate
during moderate exercise <110 beats per minute).
Primary outcome was a composite of death from cardiovascular causes,
hospitalization for heart failure, and stroke, systemic embolism, bleeding, and
life-threatening arrhythmic events.
The duration of follow-up was at least 2 years, with a maximum of 3 years.
Results:
Primary outcome at 3 years was 12.9% in the lenient-control group and 14.9%
in the strict-control group. (90% confidence interval, –7.6 to 3.5; P<0.001 for
the prespecified noninferiority margin).
The frequencies of the components of the primary outcome were similar in the
two groups. More patients in the lenient-control group met the heart-rate target
or targets 97.7% vs. 67.0% in the strict-control group; P<0.001 with fewer total
visits (75 vs. 684]; P<0.001). The frequencies of symptoms and adverse
events were similar in the two groups.
Conclusions: In patients with permanent atrial fibrillation, lenient rate control
is as effective as strict rate control and is easier to achieve.
Van Gelder, et.al, for the RACE II Investigators NEJM April 15, 2010, No. 15, Vol 362: 1363-1373
Atrial fibrillation
Rate control – Drug Therapy:
Digoxin – controls resting rate, OK in CHF patients .
Beta, Ca+2 blockers – controls resting and exercise
rates.
Best therapy – combination of beta blocker and
digoxin.
Even in the best of circumstances pacing support is
sometimes required
Goal: Chronic afib – mean 24hr HR < 80-90 bpm (?)
APPROACHES TO AF THERAPY
Rate control plus
anticoagulation preferred
•
•
•
•
•
•
No or lesser AF symptoms
Longer AF Hx
More SHD
Toxicity Risk
Elderly
Greater risk of
proarrhythmia
Rhythm control
preferred
•
•
•
•
•
Greater AF symptoms
Symptoms despite rate control
Younger age
No or lesser SHD
Rx option of class IC AAD
In anticoagulation candidates, continue anticoagulation indefinitely
Atrial Fibrillation
Length of time
in AF prior to
cardioversion
•
Duration of
AF is the best
predictor of
recurrent AF
after
cardioversion
Patients in sinus rhythm (%)
100
< 3 Months
3 - 12 Months
> 12 Months
80
60
40
*
20
0
*P = <0.02
Initial
Dittrich HC. Am J Cardiol. 1989;63:193-197.
One month
post-CV
Six months
post-CV
Rhythm Control for AF: Commonly
Used Oral Antiarrhythmic Drugs
Class IA
Class IC
Class III
Quinidine
Propafenone
Sotalol
Procainamide
Propafenone SR
Amiodarone
Disopyramide
Flecainide
Dofetilide
Procainamide, disopyramide, and amiodarone are not FDA-approved for
treatment of AF.
Miller and Zipes. In: Braunwald, et al (eds). Heart Disease. 6th ed. 2001.
AF Efficacy:
Maintaining NSR > 6 Months
70
60
NSR, %
50
40
30
20
10
0
No
drug
Quin
Diso
Prop
Flec
Sot
Dof
Azim Amio
ORGAN TOXICITY
• Examples:
– Lupus, agranulocytosis, thrombocytopenia, optic
neuritis, pulmonary fibrosis, hepatitis, etc.
• Negligible:
– Dofetilide, flecainide, propafenone, sotalol,
dronedarone
• Acceptable:
– Azimilide, disopyramide
• High:
– Amiodarone, procainamide, quinidine
Drug-Induced Proarrhythmia - Torsades
Factors Which Influence
Ventricular Proarrhythmia Risk
•
•
•
•
•
•
•
Hypokalemia, hypomagnesemia
Long QT at baseline
CHF / Decreased EF / Ventricular hypertrophy
Bradycardia
Female gender
Reduced drug metabolism or clearance
Amiodarone and Dronedarone has lowest risk
(drondedarone cannot be started if baseline QTc>/=500)
AARx Choice
Heart disease
Antiarrhythmic
None
Vagal afib
HTN
IC or Dronedarone
Disopyramide
IC (if no sig. LVH)
then dronedarone
Sotalol
Amiodarone
CAD
CHF/Substantial
LVH
Prevention of atrial fibrillation by ReninAngiotensin system inhibition
Meta analysis of published clinical trial data on the effects of renin-angiotensin system (RAS)
inhibition for the prevention of atrial fibrillation
A total of 23 randomized controlled trials with 87,048 patients were analyzed.
In primary prevention: 6 trials in hypertension, 2 trials in myocardial infarction, and 3 trials in
heart failure were included.
In secondary prevention: 8 trials after cardioversion and 4 trials assessing the
medical prevention of recurrence were included.
Overall, RAS inhibition reduced the odds ratio for AF by 33% (p < 0.00001), but there was
substantial heterogeneity among trials.
In primary prevention:
RAS inhibition was effective in patients with heart failure and those with hypertension and left
ventricular hypertrophy but not in post-myocardial infarction patients overall.
In secondary prevention:
RAS inhibition was often administered in addition to antiarrhythmic drugs, including
amiodarone, further reducing the odds for AF recurrence after cardioversion by 45% (p =
0.01) and in patients on medical therapy by 63% (p <0.00001).
RAS inhibition is an emerging treatment for the primary and secondary prevention of AF
Schneider MP, et. Al. J Am Coll Cardiol. 2010 May 25;55(21):2299-307
Alternatives to Drug therapy
“Non-Pharmacologic Therapy”
Coumadin – LAA closure (Watchman)
Rate Control – AVN RFA + PCMK
AARx – Adjunctive AFL RFA
AARX – Curative Afib RFA
WATCHMAN® LAA Filter
System
Complete AVN ablation
Pacemaker Placement
AVN RF ablation
Objective Benefits of AV nodal Ablation
70
55
50
mean
54 + 7
60
mean
34 + 5
LVESD (mm)
LVEF (%)
45
50
mean
43 + 8
40
p < 0.001
30
40
mean
40 + 5
35
30
p < 0.003
25
20
20
Before
After
A Left ventricular ejection
fraction (%)
Rodriguez LM. Am J Cardiol. 1993;72:1137-1141.
Before
After
B Left ventricular end systolic
diameter (mm)
Complete AVN Ablation
Advantages:
100% efficacy
85% symptomatic improvement
Improved EF (LV remodeling)
Eliminates need for rate control drugs
Disadvantages:
Pacemaker dependant
Good Candidates:
Tachy / Brady Syndrome
PCMK in Place – CHF with BiV device
Medication refractory / intolerant
Elderly
60 F with PAF treated with Rythmol
Presented with recurrent tachycardia
Atrial Flutter Circuit
Atrial Flutter Circuit
Atrial Flutter Ablation
Atrial Flutter RFA
Atrial Flutter Ablation
Approximately 15% of AF patients treated with an AA
will develop AFL
Advantages:
95% efficacy
≈ 80% arrhythmia control if AARx continued
As primary Rx: RFA more effective than AARx
Disadvantages: Invasive
Good Candidates:
Typical AFL (IVC / TV isthmus)
Primary AFL or AARx related AFL
Focal Origin of Atrial
Fibrillation
Hassaiguerre M, NEJM, 1998
• 94% of AF triggers
from Pulmonary
Veins
• “90 – 95% of all AF
is initiated by PV
ectopy”
RA
LA
SVC
17
31
FO
Pulmonary
Veins
6
IVC
CS
11
74 yo medically refractory AF, Echo – Normal
AA Rx - Verapamil, Rythmol, Betapace, Norpace
I
II
III
V1
RSPV
dist
RSPV
prox
LIPV
RA
*
Lasso Catheter
Circular Mapping & Ablation Catheter in
Right Superior Pulmonary Vein
Atrial Fibrillation Ablation
Atrial Shell and Cardiac MRI
45 yo F with medically refractory
Highly Symptomatic PAF
45 yo F with Medically Refractory PAF
CT Scan / Carto Images – PA View
45 yo with PAF
Conversion of AF to NSR, LSPV with AF
Abl
Lasso
LSPV
CS
Current State of Curative
Catheter-Based RFA
Procedural Success & Complications
• Total Patients > 1300 (65% PAF)
• Expected success @ 1yr
– ≈ 70% after first procedure
– ≈ 80% after second procedure
• Complications ≈ 1 to 3%
–
–
–
–
–
Tamponade – 0.6%
Pulmonary vein stenosis – 0.6%
TIA / CVA – 0.5%
Esophageal-LA fistula - 0
Groin Bleeding / Hematoma
(Last 200 pts complications < 1%)
Atrial Fibrillation: Ablation vs Drug Rx.
Ablation
80% success
PV stenosis
AE fistula
TIA/CVA
Drug Rx.
50% success
Proarrhythmia
End Organ Toxicity
No Free Lunch
Torsades
AE fistula
PV stenosis
Current State of Curative
Catheter-Based RFA
Who is a good candidate?
Symptomatic / Frequent AF
Limited Heart Dz
EF > 35%
LA < 5.5cm
No MS / Rheumatic Dz
Younger Patients
No LA thrombus or Hx of CVA
Medically Refractory / Intolerant
(Ablation now second line therapy)
Atrial Fibrillation
New Technology Coming Your Patients Way at
Ohio State University
Stereotaxis – Magnetic Catheter Navigation
Ablation Frontiers
Cryoablation Balloon
Endosense
A-Fib vs. EP Labs
AF TREATMENT GOALS
• AF is rarely life-threatening and is
typically recurrent
• Treatment goals in symptomatic pts
–  frequency of recurrences
–  duration of recurrences
–  severity of recurrences
• Minimize risk of tachycardia induced
cardiomyopathy
• Safety is primary concern