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Transcript
Current Management of Atrial Fibrillation:
An Evidence-Based Approach
John D. Hummel, MD
Ohio State University Medical Center
Ross Heart Hospital
Columbus, Ohio
Learning Objectives
• Understand the guidelines for
anticoagulation and where there is
latitude for physician decision making.
• Be able to discriminate between
patients requiring restoration of sinus
rhythm vs. rate control alone.
• 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
•
•
•
•
•
•
•
•
•
•
Minimum Evaluation
History and physical – Sx with AF, CV dz
Electrocardiogram – WPW, LVH, MI
Echocardiogram – LVH, LAE, EF, Valve Dz
Labs – TSH, Renal fxn, LFTs
Additional Testing
ETT – CAD, Exercise induced SVT / AF
Holter / Event Monitor – Confirm AF and Sxs
TEE – LA clot
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
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=2
Previous CVA / TIA / Embolism
Mitral Stenosis
Prosthetic heart valve
Moderate-Risk Factors=1
Age > 75 yrs
HTN
CHF
DM
EF < 35%
Weaker-Risk Factors~½
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
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.
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
AF Rate vs. Rhythm Control Trials:
Implications
• AFFIRM has demonstrated that rate control is
an acceptable primary therapy in a selected
high-risk subgroup of AF patients
• Continuous anticoagulation seems warranted
in all patients with risk factors for stroke
– Asymptomatic recurrences
• Is there a role for rhythm control?
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
Impact of AF on Risk of Death: Framingham Heart Study
Kaplan-Meier mortality curves for age and sex matched subjects (independent of cardiac conditions and risk factors)
Benjamin, E. J. et al. Circulation 1998;98:946-95
Improvement in Left Ventricular (LV) Function and Dimensions after Ablation in Patients with
Congestive Heart Failure
Hsu, L. et al. N Engl J Med 2004;351:2373-2383
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.
ORGAN TOXICITY
• Examples:
– Lupus, agranulocytosis, thrombocytopenia, optic
neuritis, pulmonary fibrosis, hepatitis, etc.
• Negligible:
– Dofetilide, flecainide, propafenone, sotalol
• 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 has lowest risk
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
Pathophysiology of AF
• Initiation
– Pulmonary vein atrial ectopy
• Maintenance
– Atrial myocardium
• Termination
Normal Sinus Rhythm
Right & Left Atria
Electrograms During AF
Surface, Right & Left Atria
Surface
Right
Atrium
Disorganized
Organized
Left
Atrium
Complex Atrial Anatomy Around
Pulmonary Veins
Beginnings of “Non Pharmacologic ”
Therapies for AFib
• Minneapolis Feb 1999
• Haisseguerre – Bordeaux, France
• Designed a circular catheter to map the
pulmonary veins
• “Pulmonary Vein Isolation”
• Atrial muscle bundles span the transition zone from
the pulmonary veins into the atria – trigger for AFib
• Ablation – use energy in the radiowave
frequency to dessicate tissue at culprit sites
Fib
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
Who Should Have Ablation
• Symptomatic Patients
• Failed Class I or III Drug therapy
• Pts. not tolerating chronic
medical therapy
Procedure
•
•
•
•
Arrive on day of procedure
“Table-time” - 4 hours
Usually discharged the next day
Limited activity for 3-5 days then
no restrictions
Success Rates
•
•
•
•
>1000 procedures
Cure rate is about 80-85% at 1 year
1.45 procedures per pt
Success rate is highly dependent on
other variables:
–
–
–
–
–
High blood pressure
Sleep apnea
Number of years with AFib
Size of the atria
Other heart disease
Complications
• Complications ≈ 1.5%
–
–
–
–
–
Tamponade – 0.6%
Pulmonary vein stenosis – 0.6%
TIA / CVA – 0.5%
Esophageal-LA fistula - 0
Groin Bleeding / Hematoma
• No deaths
• No inadvertent damage to the
esophagus
(Last 200 pts complications < 1%)
New Technology Coming to Increase Efficacy
and Decrease Risk of Complications
Stereotactic – Magnetic Catheter Navigation
Energy Sources
High Intensity Focused Ultrasound (HIFU)
Cryoablation
Lasar
Left Atrial Appendage Closure
Stereotactic
Navigation
Automatic Catheter Access to Pulmonary Veins
Automatic Catheter Access to Right Inferior
Pulmonary Vein
Point and Click: Mapping Near
Site of Early Activation
Atrial Fibrillation Ablation
Evolution of the Moving Target
Esophageal
Fistulas
Left Atrial
Flutters
Tamponade
TIA/CVA
Early Rumors
(20 hr cases)
Mid 90’s
Left Sided Focal
IVUS / Transeptal
Right Sided Linear
WACA + Linear
Lasso
Hybrid Approaches
3D Mapping CT integration
2006
Fractionated Egms
PV Isolation
PV Stenosis
Phrenic Nerve
Injury
The Trouble With a Moving Target
Back to the
Right Side
Need for Stereotaxis,
Cryoablation, HIFU?
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
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