atrial fibrillation nora goldschlager, m.d. macp, facc, faha, fhrs cardiology – san francisco...
TRANSCRIPT
ATRIAL FIBRILLATION
Nora Goldschlager, M.D.MACP, FACC, FAHA, FHRS
Cardiology – San Francisco General HospitalUCSF
Disclosures: None
INCREASING PREVALENCE OF AF
2005 2015 2025 2035 2045
Naccarelli et al AJC 2009;104:15334Reuters database, US Census Bureau Projected Estimates
Year
Ind
ivid
ual
s w
ith
AF
on
ly(m
illio
ns)
8
6
4
2
0
All
Men
Women
INCIDENCE
• Occurs in ≥ 2% of population(more than 5 million pts in US;
projected >10 million by 2050)• Prevalence increases with age
1% in people > 60 5 - 6% of people > 6514% of people > 80
• Associated with > 100,000 strokes / yr• Develops in 10 - 30% of pts with
LV dysfunction; is a predictor of mortality (1 - 3x)
• RR for death 1.5 (men) and 1.9 (women)
CONSEQUENCES OF AF IN THE US:US DATABASE ANALYSIS
350,000 hospitalizations/yr7 million office visits/yr542,000 ED visits/yr$6.42 billion annually
Coyne et al Circulation 2004; 110:III - 826Zimetbaum, Circulation 2005; 111:3141
Types
• Paroxysmal – Self-terminating• Persistent – Requires cardioversion
to restore sinus rhythm• Permanent – Complete inability to
maintain sinus rhythmEtiologies
• Rheumatic• Nonrheumatic• Lone
CLASSIFICATION
ASYMPTOMATIC ATRIAL FIBRILLATION
• Incidence 20 - 50%
• Most asymptomatic pts have chronic AF
• Up to 50% of pts with paroxysmal AF have no symptoms (pacemaker stored data)
• Occurs in up to 20% of pts with no AF history (ICD stored data)
• Is present in up to 30% of pts presenting with stroke without AF history
Risk of AF in systolic dysfunction
• Men 4.5x• Women 5.9x• Whites 38%• AA 20%• NYHA I-II 10%
IV 50%
AF in diastolic dysfunction
• Prevalence ~ 10%• Risk related to degree of
diastolic dysfunction (echo) -
hazard ratio 3.3 5.3
AF IN HEART FAILURE
NEW YORK HEART ASSOCIATION FUNCTIONAL CLASS
Pre
vale
nce
of
AF
(%
)
60
40
20
0
I II-III III-IV IV
Maisel, Stevenson AJC 2003;91:2-8
SOLVD prevention
SOLVD treatment
V-HeFT
CHF-STAT
DIAMOND CHP
GESICA
CONSENSUS
DOES AF INCREASE CHF MORTALITY?
Framingham Study: evaluated temporal effect ofdevelopment of AF or CHF on mortality
Mortality HR (95% Cl)Men Women
Patients with AF
Add CHF 2.7 (1.9 - 3.7)
3.1 (2.2 - 4.2)
Patients with CHF
Add AF 1.6 (1.2 - 2.1) 2.7 (2.0 - 3.6)
Wang et al. Circulation 2003;107(23)2920-2925
• Incidence:AA (n = 223) - 20%Caucasian - 38%
• AA: younger (67 vs 74, p .001)HT (87% vs 78%, p .01)Prior CHF (79% vs 71%, p .01)Less CAD Dx
• AA lower odds of AF (49%) after adjustment for EF, age, gender, meds, DM, CHF etiology
Ruo et al JACC 2004; 43:429 EPOCH study patients N = 1373; 37% with AF Kaiser database
AF AND RACE IN PATIENTS HOSPITALIZED WITH CHF Dx
AF IN WOMEN
• Although risk is higher in men, 53% of all AF pts are women
• Women with CHF have 14x risk of AF, 8.5x risk in men
• Suggestion that embolism in women > men
• More sx, higher VR
• Higher proarrhythmia risk with AARx
19.2 %
EFFECT ON MORTALITY OF AF IN HEMODIALYSIS PTS (INDEPENDENT OF EF)
Cu
mu
lati
ve s
urv
ival 1.2
.8
.4
00 10 20 30 40 50
MosVazquez et al AJC 10.1.03 N = 190
71.3 %SRN=164
AFN=26
c
INFLAMMATION AS A RISK FACTOR FOR AF
Aviles et al Circulation 2003;108:3006 N = 5806 Cardiovascular Health Study (5% AF at baseline)
AF
fre
e su
rviv
al (
%) 100
95
90
85
800
Pts w/CRP level < median (1.92 mg/liter)
Pts w/CRP level > median (1.92 mg/liter)
0 1 2 3 4 5 6 7Yrs
OBSTRUCTIVE SLEEP APNEA AND INCIDENT AF
JACC 2007;49:565
0 2 4 6 8 10 12 14
OSA
No OSA
15
10
5
0Cu
mu
lati
ve f
req
uen
cyo
f A
F (
%)
Years
POTENTIAL MECHANISMS OF ASSOCIATION OF AF AND OSA
• Diastolic dysfunction with increase in LA size• Negative intrathoracic pressure fluctuations
leading to transmural pressure changes and wall stress
• Ion channel changes– stretch-sensitive– catacholamine-sensitive (apnea-related
increase)– vagal tone increase (end-apneic periods)
• Systemic inflammation associated with OSA• Hypoxemia• Hypercarbia• sympathetic drive
AF DURING ACUTE MIIncidence: 11% on entry
11% during hospitalizationCorrelations: Age
Anterior MIKillip IVPrior MICHF*
Outcomes:Higher death rates (indep. predictor)
- In hospital* 25% (vs 16% no AF)- 30 days* 29% (vs 19%)- 1 yr 48% (vs 33%)
Reinfarction* Higher in AF developing during MI
Rathmore et al, Circulation 3.00, N = 106,780 medicare pts 65 yo ((79)>
AF AND SUDDEN CARDIAC DEATH MORTALITY
• In the AVID Registry, AF present in 23% of patientsAF independent risk factor of SCD mortality (RR=1.20; P=.02)
• In MUSTT and MADIT II, AF was the second largestindependent risk factor for SCD
• CASS Registry: AF independent risk factor for SCD
• V-HeFT I and V-HeFT II: no correlation betweenmortality and AF
The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators.N Engl J Med. 1997;337:1576 Wyse et al. J Interv CardElectrophysiol. 2001;5:267 Zareba. Presented at NASPE 23rd
Scientific Session; May 2002 Cameron el al. Am J Cardiol. 1988;61:714
MANAGEMENT OPTIONS IN AF
Ventricular rate controlCA++ -blockers-blockersDigoxinAVN ablation
Restoration of NSRElectrical conversion Antiarrhythmic drugs
Maintenance of NSRAntiarrhythmic drugsDual chamber pacingAtrial overdrive pacingDual site atrial pacingAtrial septal pacingAF ablation
REASONS TO PERFORM EARLY RESTORATION OF NSR IN PTS WITH AF
• The longer the AF duration, the higher energy levels (transthoracic and internal) required for cardioversion
• Repeated atrial burst pacing leads to longer episodes of AF, eventuating in chronic AF (goats)
• The longer the AF episodes, the greater the atrial EP and histologic pathology
ANTIARRHYTHMIC DRUGS TO MAINTAIN SINUS RHYTHM
% of pts in Agent sinus rhythm at 1yr
• None 25%• Class 1A, and Sotalol 50%• Class 1C (propafenone,
flecainide) 50 - 60%• Dofetilide ~ 60%• Amiodarone 70 - 80%
• Dronedarone about 60%
Failure to convert AF to NSR does not mean that drug will not maintain NSR once it is achieved
EVALUTION OF AARx THERAPYTO MAINTAIN SR
• Time to 1st AF recurrence (should not be sole criterion of drug failure)
• Frequency of AF recurrences
• Duration of AF recurrences
• Symptoms during AF recurrences
AF: POST CONVERSION SR vs AFAND SERUM ALDOSTERONE LEVELS
SerumAldo(pg/ml)
200
150
100
50
0
Wozakowska-Kaplon et al PACE 2010; 33:561
SR maintained
AFrecurrence
24 h before CV24 h after CV
EURIDIS/ADONIS• Patient enrollment: 1237 patients
• Inclusion criteria: Presence of paroxysmalor persistent AF or AFL, with ≥ 1 documentedepisode in the 3 months prior to enrollment,and in normal sinus rhythm for at least 1 hour
• Primary endpoint: Time from randomizationto first AF/AFL recurrence
• Study medication: Dronedarone 400 mg BIDor placebo for 12 months
• Results: Dronedarone prolonged time to first recurrence of AF/AFL
Combined RR reduction: 25%Absolute RR reduction: 11% at 12 months
N Engl J Med 2007;357:987-999
DRONEDARONE*EURIDIS AND ADONIS TRIALS
• incidence of 1st (symptomatic) AFrecurrence
• VR during AF recurrences• hospitalization or death rates
(also ATHENA trial)• No substantial effect on QT interval
(? Atrial selectivity)• Low Torsades de pointes risk• Avoid in HF patients (ANDROMEDA study)
* Multiple ion-channel blockade; half-life 1-2 days
0 60 120 180 270 360
No. at risk
Placebo 409 192 156 133 112 90Dronedarone 828 450 389 347 307 262
DRONEDARONE FOR SR MAINTENANCE IN AF AND FLUTTER
Days
Singh et al NEJM 2007; 357:987
Cu
mu
lati
ve
in
cid
en
ce
(%
)80
60
40
20
0
Placebo
Hazard ratio, 0.75
P < 0.01
Dronedarone
ATHENA: OVERVIEW - 1
• Objective
A multicenter, multinational, double-blind, randomized placebo-controlledstudy of dronedarone in 4628 patientswith a recent history of AF/AFL who werein sinus rhythm or who were to be converted to sinus rhythm to assess theefficacy of dronedarone 400 mg bid for the prevention of cardiovascularhospitalization or death from any cause
Hohnloser SH et al J Cardiovasc Electrophysiol. 2008;19:69-73Hohnloser SH et al N Engl J Med 2009;260:668-678
ATHENA: OVERVIEW - 2
• Patients representative of general AFpopulation
– History of paroxysmal or persistent AF/AFL– Aged ≥ 75 years with or without additional
risk factors
– Aged ≥ 69 years and ≥ 1 risk factor (HT, DM prior CVA/TIA, LA diameter ≥ 50 mm, LVEF < 40)
Hohnloser SH et al J Cardiovasc Electrophysiol. 2008;19:69-73: N Engl J Med 2009;260:668-678
ATHENA: OVERVIEW - 3
• Primary endpoint: Time to first CV hospitalization or death from any cause
• Secondary endpoints: All-cause mortalityCV hospitalization
Hohnloser SH et al J Cardiovasc Electrophysiol. 2008;19:69-73;N Engl J Med 2009;260:668-678
ATHENA: SUMMARY
• Dronedarone significantly prolongs timeto first CV hospitalization in patients withparoxysmal or persistent AF andassociated CV risk factors
• Reduction in CV hospitalization mainly dueto admissions for AF
• The 24% reduction in cardiovascular hospitalization or death from any cause wasgenerally consistent in all subgroups based on baseline chracteristics ormedications
0 6 12 18 24 30
No. at risk
Placebo 2327 1858 1625 1072 385 3Dronedarone 2301 1963 1776 1177 403 2
ATHENA: DRONEDARONE AND CV EVENTS IN AF
Primary outcome (1st hospitalization due to CV events or death)
Mos
Hohnloser et al NEJM 2009; 300:668
Cu
mu
lati
ve
in
cid
en
ce
(%
)
50
25
0
Placebo
P < 0.001
Dronedarone
0 6 12 18 24 30
No. at risk
Placebo 2327 2290 2250 1629 636 7Dronedarone 2301 2274 2240 1593 615 4
ATHENA: DRONEDARONE AND CV EVENTS IN AFDeath from CV causes
Mos
Hohnloser et al NEJM 2009; 300:668
Cu
mu
lati
ve
in
cid
en
ce
(%
)
5.0
2.5
0
P < 0.03Dronedarone
Placebo
ANDROMEDA: OVERVIEW -1
• Designed to evaluate dronedarone,400 mg BID, on all-cause death orhospitalization for worsening heart failure
• Enrolled 627 of 1000 patients (310 and 317in the dronedarone and placebo groups,respectively)
• Patients had relatively severe heart failureand had been hospitalized, or referred to aspeciality heart failure clinic for worseningsymptoms
Kφber L: et al N Engl J Med 2008;358:2678-2687
ANDROMEDA: OVERVIEW - 2
• 38% of subjects had a history of AF/AFLand 25% had AF/AFL at enrollment
• Primary composite endpoint : all-causemortality or hospitalization for heartfailure
• Trial terminated because of a two-foldincrease in mortality in dronedaronegroup
Kφber L: et al N Engl J Med 2008;358:2678-2687
ACC / AHA / ESC GUIDELINES:RISK-STRATIFIED ANTITHROMBOTIC Rx
Risk factors: HF, LV EF 0.35, Hx HT
Fuster et al Eur Heart J. 2001;22:1852-1923
Age < 60, no HDAge < 60 + HD, no risk factorsAge > 60Age 60, DM or CAD
Any age + risk factors or thyrotoxicosis
Rx
ASA (325 mg/d or no Rx)ASA (325 mg/d) Warfarin (INR 2.0 - 3.0)Warfarin (INR 2.0 - 3.0) low dose ASA (class IIb) Warfarin (INR 2.0 - 3.0)
ACC / AHA / ESC GUIDELINES:RISK-STRATIFIED ANTITHROMBOTIC Rx
Risk factors: HF, LV EF 0.35, Hx HT
Rx
Age 75 (pts c risk Warfarin (INR -2.0) bleed - esp )
Rheumatic HD, prosthetic Warfarin (INR 2.5-3.5 heart valves, prior or higher maythromboembolism, be appropriate)persistent atrialthrombus on TEE
Fuster et al Eur Heart J 2001;22:1852-1923
RISK STRATIFICATION FORANTICOAGULATION IN AF:
CHADS2 Score
Points
• Congestive heart failure 1• Hypertension 1• Age 75 years or older 1• Diabetes mellitus 1• Stroke or TIA history 2
Gage BF et al JAMA 285: 2864-2870; 2001
ANTICOAGULATION RECOMMENDATIONS BY CHADS2 SCORE
• CHADS2 0– Low risk (0.5%/yr)– ECASA 325 mg qd
• CHADS2 1-2– Intermediate risk (1.5-2.5%/yr)– Warfarin (INR 2.0-3.0) > ECASA 325 mg qd
• CHADS2 3– High risk (5.3-6.9%/yr)– Warfarin (INR 2.0-3.0) unless contraindicated
VITAMIN K ANTAGONISTS IN AF
• Reduce stroke by 38%, compared to aspirin
• Recommended in high risk patients with AF
• Only 40-50% of ideal patients receive VKA in Western countries
–Many patients considered unsuitable
–Due to poor INR control, concern about bleeding
–Patient preference
In patients with AF, unsuitable for VKA therapy, addition of clopidogrel to aspirin will reduce the risk of major vascular events, at acceptable risk of major bleeding
HYPOTHESIS OF ACTIVE A
• All patients received aspirin at a recommended daily dose of 75-100 mgs
• Patients were randomized, double blind, to clopidogrel, 75 mg per day, or matching placebo
ACTIVE A - STUDY TREATMENT
OUTCOMES AND STATISTICAL POWER
• Primary outcome was a composite of major vascular events:
–Stroke, myocardial infarction, non-CNS systemic embolism or vascular death
• Secondary outcomes
–Stroke
–Major hemorrhage
• 7500 patients planned to achieve 88% power to detect 15% reduction in primary outcome (1600 events)
STUDY CONDUCT
• 33 Countries, 580 centers
• 7554 patients enrolled between
June 2003 and May 2006
• Final follow up in November 2008
–Median follow up 3.6 years
–Follow up was complete in
99.4% of patients
BENEFITS AND RISKS: COMPARED TO WARFARIN
Effects
WarfarinversusAspirin
Clopidogrel & AspirinversusAspirin
Meta-analysis*(RRR)
ACTIVE A(RRR)
Reduction in stroke - 38% -28%
Increase in intra-cranial bleed +128% +87%
Increase in extra-cranial bleed +70% +51%
*Hart RC et al. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have non-valvular AF . Ann Intern Med 2007: 146: 857-67
RE-LY: A Non-inferiority Trial
Atrial fibrillation ≥1 Risk Factor
Absence of contra-indications951 centers in 44 countries
R
Warfarinadjusted
(INR 2.0-3.0)N=6000
Dabigatran Etexilate
110 mg BIDN=6000
Dabigatran Etexilate
150 mg BIDN=6000
Blinded Event Adjudication.
Open Blinded
RE-LY: A Non-inferiority Trial
Atrial fibrillation ≥1 Risk Factor
Absence of contra-indications951 centers in 44 countries
R
Warfarinadjusted
(INR 2.0-3.0)N=6000
Dabigatran Etexilate
110 mg BIDN=6000
Dabigatran Etexilate
150 mg BIDN=6000
Blinded Event Adjudication.
Open Blinded
Ischemic/Unspecified Stroke
D 110 mg vs. Warfarin
D 150 mg vs. Warfarin
RR =1.1195% CI = 0.89-1.40P = 0.35
RR = 0.7695% CI = 0.60-0.98P = 0.03
Years of Follow-up
Cu
mu
lati
ve H
azar
d R
ates
0.0
0.02
0.04
0.06
0.08
0 0.5 1.0 1.5 2.0 2.5
Dabigatran110
Dabigatran150
Warfarin
Hemorrhagic Stroke
D 110 mg vs. Warfarin
D 150 mg vs. Warfarin
RR = 0.31
95% CI =0.17-0.56
P <0.001
RR =0.26
95% CI =0.14-0.49
P <0.001
Years of Follow-up
Cu
mu
lati
ve H
azar
d R
ates
0.0
0.01
0.02
0.03
0.04
0 0.5 1.0 1.5 2.0 2.5
Dabigatran110
Dabigatran150
Warfarin
Rhythm Control • Loss of AV synchrony may produce sx • Prevents remodeling effects of AF • May play a role in stroke prevention
Rate Control • Anti-arrhythmic therapy is only
~ 60% effective long-term • Pro-arrhythmia and other side-effects • Many symptoms are relieved with
adequate control of rate
RATIONALE:RATE CONTROL vs RHYTHM CONTROL
ADVANTAGES OF RATE CONTROLVS RHYTHM CONTROL - 1
• Rate control (with anticoagulation):- No or few Sx of AF- Greater degree of structural heart
disease (e.g., requiring amiodarone)- Adverse response to AA Rx- Greater risk of proarrhythmia
EFGenderQT
ADVANTAGES OF RATE CONTROLVS RHYTHM CONTROL - 2
• Rhythm control:- Sx with AF that impact QOL- Sx despite adequate rate control- Young age- No or little structural heart disease- No or immediate need for AA Rx with
significant side effect profile- Contraindication to anticoagulation- 1st AF episode
AF FOLLOWUP INVESTIGATION OF RHYTHM MANAGEMENT (AFFIRM) TRIAL
Inclusion criteria:• 65 y.o. or other risk factor for stroke or
death*; 6 hrs AF in past 6 mos• FU 3.5 y• Rate control group 80/min rest, 110/min
with 6 min walk• End points
1º - overall mortality2º - composite: death, stroke, bleed,
cardiac arrest
* HT 70%, CAD 38%, LAE 65%, prior TIA, CHF 24%, avg EF 55%
NEJM 12.5.02 N = 4060 enrolled, 7401 screened
>
<
>
AF FOLLOWUP INVESTIGATION OF RHYTHM MANAGEMENT (AFFIRM) TRIAL
Cu
mu
lati
ve
mo
rtal
ity
(%)
20
10
0Deaths: 0 1 2 3 4 5No. (%) YearsRhythm control 0 80 (4) 175 (9) 257 (13) 314 (18) 352 (24)Rate control 0 78 (4) 148 (7) 210 (11) 275 (16) 306 (21)
NEJM 12.5.02
Rate control
Rhythm control
p = 0.08
AFFIRM: ADVERSE EVENTSRate Rhythm
control control
Ischemic stroke 79 (5.7%) 84 (7.3%)
INR 2.0 24 (30%) 18 (22%)
INR < 2.0 28 (35%) 17 (20%)
Not taking 26 (33%) 48 (58%)warfarin
AF at time 45 (69%) 25 (36%)of event
>
AFFIRM: LIMITATIONS
• Enrolled older, high risk pts• Chronic or paroxysmal AF could be enrolled;
PAF pts in rate control arm may have had NSR at times (52% of pts in rate control arm were in NSR at randomization); some pts in rhythm control arm likely had AF at times
• AF recurrences and durations not known over time in rhythm control group; periods of NSR not known in rate control group
AFFIRM IMPLICATIONS I
• Studied patients presumably required long-term Rx and had risk factors for stroke
• Coumadin should be continued in patients who are thought to be rhythm controlled
• AA drugs are not an alternative to coumadin
AFFIRM IMPLICATIONS II• Rate control carries no higher mortality or
lower functional benefit over rhythm control
• Did not answer the question of whether SR is better than AF with rate control
• Compared current pharmacologic strategies– Imperfect rhythm control– Incomplete monitoring of rhythm (single
ECG at FU; no Holter data)• Decision to rate or rhythm control should be
based on symptoms
POTENTIAL NEW MANAGEMENT STRATEGIES IN AF
AND PTS AT RISK FOR AF
ACE inhibitorsARBsAntiinflammatory agents
ASAStatinsFish oil
EFFECT OF ENALAPRIL ON AF INCIDENCE* IN PTS WITH LV DYSFUNCTION (SOLVD STUDY)
Fre
edo
m f
rom
AF
1.0
.75
.50
0
* Most episodes were paroxysmal
Vermes et al Circulation 2003;107:2926-2931AF developed in 55 / 374
Enalapril n = 186 (5%)
Placebo n = 188 (24%)
Risk reduction 19%
0 1 2 3 4 5Time (yrs)
POSSIBLE EFFECT ON ATRIAL REMODELING IN AF BY AT RECEPTOR BLOCKERS*
Pts free of AFrecurrences (%)
.0
.9
.8
.7
.6
.50 60 120 180 240 300 360
Amio + Irbesartan 150-300 mg/d
Amio 400 mg
FU (days):
Madrid et al Circulation 2002;106:331 N = 154
* Effects: Reduction of fibrosis Prevention/reduction of apoptosis
Less shortening of atrial refractory period during rapid atrial rates
HT AND NEW-ONSET AF (LIFE STUDY)P
rop
ort
ion
of
pts
w
ith
fir
st e
ven
t (%
) 8
6
4
2
00 12 24 36 48 60
Months
Wachtell et al JACC 2005; 45:712 N = 9193, 150 Losartan, 221 Atenolol
HR: 0.67, p<0.001
LosartanAtenolol
HT AND AF (LIFE STUDY):SUMMARY OF RESULTS
• Results of AF outcomes are independent of BP reduction
• AF increases cardiac morbidity/mortality in HT with LVH
• Losartan reduces AF recurrence risk in pts with AF history
• Losartan reduces incidence of new-onset AF (33%)
• Potential mechanisms- LV and LA hypertrophy regression - Atrial remodeling reversal- Reduction in atrial fibrosis
0 2 4 6 8 10 12
No. at risk
Placebo 720 520 454 407 377 344 254Valsartan 722 524 465 423 383 356 260
VALSARTAN AND 1st AF RECURRENCE
Mos since randomization
Gissi - AF NEJM 2009; 360:16
Pro
ba
bili
ty o
f 1
st
AF
re
cu
rre
nc
e
N = 1,442 CVD, DM or LAE;LVEF > 40% in > 90%; Lone AF ~ 10%; 70% on AARxP = 0. 83
.6
.4
.2
0
PlaceboValsartan
STATIN USE AND IN-HOSPITALARRHYTHMIAS IN ACS
Vedre et al, GRACE registry 1999-2007AJC 2009;104:1613 N=64, 679, 27% statin use
Pat
ien
ts (
%)
10
8
6
4
2
0VT/VFCA AF/flutter Hospital
death
4.3
7.4 6.98.2
3.2
5.5
Prior statin No prior statin
NEW-ONSET AF AFTER HOSPITAL ADMISSION FOR CAD STRATIFIED BY STATIN USE WITHIN
ONE MONTH OF HOSPITAL DISCHARGE
Kulik et al AJC 2010; 105:1655 Medicare database 1995-2004 N = 29,088
Inci
den
ce o
fN
ew A
F (
%)
100
50
00 60 120
Months post-dischargeAt risk:Statin 8,450No statin 20,638
2,2476,711
146841
Adjusted HR 0.90 ± 0.03 P = 0.0006
No Statin Statin 5 y: 38.3% 32.6%10y: 58.0% 51.2%
Statin n/M Control n/M OR 95% Cl OR
MIRACL 93/1539 96/1548 0.97Tveit 18/51 17/51 1.09Dernellis 14/40 36/40 0.06ARMYDA3 35/101 56/99 0.41Chelio 2/20 5/20 0.33Ozaydin 3/24 11/24 0.17
P = .02 0.39
META-ANALYSIS OF RCTS: EFFECT OF STATINS ON AF
Fauchier et al JACC 2008; 51:828
.02 1 2 5
Rx Control Favors
All AF
META-ANALYSIS OF RCTS: EFFECT OF STATINS ON AF
Primary prevention (post-operative or new onset AF)
Statin n/M Control n/M OR 95% Cl OR
MIRACL 1 25/1421 23/1440 1.10ARMYDA 3 35/101 56/99 0.41Chelio 2/20 5/20 0.33
P = NS 0.60
Fauchier et al JACC 2008; 51:828
.02 1 2 5
Rx Control Favors
META-ANALYSIS OF RCTS: EFFECT OF STATINS ON AF
AF Recurrence (FU ≥ 6 wks)
Fauchier et al JACC 2008; 51:828
.02 1 2 5
Rx Control Favors
Statin n/N Control n/N OR 95% Cl OR
MIRACL 2 68/118 73/108 0.65Tveit 18/51 17/51 1.09Dernellis 14/40 36/40 0.06Ozaydin 3/24 11/24 0.17
P = .06 0.33
POTENTIAL CANDIDATES FOR CURATIVE AF ABLATION:
PATIENT CHARACTERISTICS
• Frequent paroxysmal AF (not persistent)
• Frequent isolated PACs on monitoring• Lone AF• Younger patient and minimal HD• Focal AF
REVIEW OF ABLATION STUDIES
• Most patients:
Young (55 y.o.)Preserved LVEF (~ 60%)LA diameter ~ 5 cm
• 1º end point usually AF recurrence(assessed by various means)
• No RCTs on stroke risk, death
• Short FU
Teresawa et al Annals Int Med 2009;151:191
PREDICTORS OF LACK OF SUCCESS OF AF ABLATION
• Persistent AF
• LA volume (>130 cc) (echo and CT)
• LA diameter >5cm (TEE)
• Low or absent voltage of atrialelectrograms (indicating scar)
LESS CONSISTENT PREDICTORSOF FAILED AF ABLATION
• LA diameter (TTE)• Hypertension• Age, gender• AF duration• Structural heart disease including
valvular disease• LVEF• DM• CAD
LEFT ATRIAL APPENDAGE OCCLUSION
• Device (WATCHMAN) must be left in theleft atrium
• Alternative: Minimally invasive epicardialablation
• NOT ALL AF ARISES FROM THE LEFT ATRIAL APPENDAGE! Up to 10% of emboli
will not be approached by this method
• May have best use in patients who arerefractory to warfarin