Management of Atrial Fibrillation in Heart Failure
Maximo Rivero-Ayerza M.D.
Clinical Electrophysiology
Ziekenhuis Oost Limburg, Genk
Objectives
• Assess the relation between AF and HF
• Try to establish the optimal treatment strategy
Prevalence
Unadjusted cumulative incidence of first AF after
Heart Failure - Framingham Study
↑ Mortality in AF:
- Men HR 1.6
- Women HR 2.7
20% of patients with HF develop AF within 4 years
Wang, T. J. et al. Circulation 2003;107:2920-2925
Prevalence
Concomitant HF: 13 % age 35 – 64 yrs
21% age > 65 yrs
Wattigneyet al. Circulation 2003;108:711-716
Prevalence
0.6
% Patients with Atrial Fibrillation
0.5
0.4
0.3
0.2
0.1
0
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LV
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prevalence increases with severity of heart failure
Class I – II
Class III - IV
Relation between AF and HF
Triggers
Atrial Fibrillation
Substrate
AF – Atrial remodeling
CHF induced followed by
5 weeks of recovery
• Irreversible induction of
fibrosis and conduction
abnormalities.
• Duration of AF was
reduced in parallel to LA
function.
Shinagawa, K. et al. Circulation 2002;105:2672-2678
Effect of intra-atrial pressure on AF
5 cm H2O
18 cm H2O
Increases in intra-atrial
pressure increases the
rate of the dominant
frequency at the level of
the PV junction compared
to LA free wall
Kalifa et al. Circulation. 2003;108:668.
Effect of intra-atrial pressure on AF
Increases in intra-atrial
pressure increases the
number of waves (rotors)
emanating from the PVs
Kalifa et al. Circulation. 2003;108:668.
Types of AF
Triggers
ectopic foci
Paroxysmal AF
Persistent AF
Electrophysiologic
Remodeling
Permanent AF
Chronic Substrate
fibrosis
Stambler et al JCE 2003;14:499
Li, Nattel et al. Circulation. 1999;100:87-95
AF – Hemodynamic Effects
*p < 0.01
N=16
NSR AF
VVI
60
VVI VVT
AVG
VVI -AVG
VVT
Clark DM. JACC 1997; 30:1039-45
Effects of AF in HF
Rapid heart rates depress contractility:
abnormal force - frequency relationship in heart failure
% change in Force
200
Nonfailing
Failing
100
0
20
60
120
180
Heart Rate (beats / min)
Mulieri Circulation 1992;
Effects of AF in HF
344 HF pts
FU= 19± 12 months
Development of AF (28 pts):
• NYHA worsened (2.4 to 2.9)
• Peak O2 consumption declined
(16 to 11 ml/kg/min)
• CI decreased (2.2 to 1.8)
• Mitral regurgitation increased
(1.8 to 2.4)
Pozolli et al. JACC 1998;31(1):197-204.
Prognostic significanse of AF
CHARM
N=
7601 pts (15% with AF)
Age= 65 y
Baseline AF
HR 1.38 (low EF)
HR 1.80 (PEF)
New onset AF
HR 2.57 (PEF)
HR 1.85 (low EF)
J Am Coll Cardiol 2006;47:1997
Prognostic significanse of AF
COMMET
N= 3029 pts (20% with AF)
Age= 62 y
Baseline AF RR=1.29 (univariate)
Baseline AF predictive of HF hosp.
New Onset AF RR=1.90 (multivariate)
Eur Heart J 2005;26:1303
Prognostic significanse of AF
DIG
N=
6800 pts (11% SVT)
Age= 63 y
RR= 2.45
CHEST 2000;118:914
Prognostic significanse of AF Epidemiological
• As many AF pts developed HF as
HF pts developed AF.
• New AF in CHF individuals was
associated with increased mortality
• Antecedent AF was not predictive
of mortality in CHF pts.
Wang TJ. Et al Circulation. 2003;107:2920
EuroHeart Failure - Mortality
P < 0.001
P < 0.001
7%
7%
12 %
13 %
In-hospital mortality
No AF
EHS-HF
Previous AF
13 %
19 %
12 week mortality
New onset AF
Rivero-Ayerza et al. submitted
Independent predictors of hospital mortality
Multiple logistic regression analysis
Less likely to die
More likely to die
New Onset AF
Previous AF
Age
Male Gender
Rapid AF
LA Dilatation
EF  50%
ACS
VHD
Renal Failure
Stroke
Elevated BP
0.1
1.5 (1.1-2.0)
1
OR (95%CI)
EHS-HF
10
Rivero-Ayerza et al. submitted
AF and HF
Summary
• AF and HF tend to coexist and share predisposing factors
• One may directly predispose to the other
• The combination of both is believed to carry a worse
prognosis then either alone.
• In the setting of HF onset of AF seems to be a stronger
predictor of adverse outcome irrespective of LV function
Management of AF in HF
Objectives
1.
Prevention of AF would be ideal
2. Avoiding hemodynamic deterioration
and improving symptoms
3.
Preventing stroke
Role of ACEI and ARB’s in prevention of AF
177 pts parox AF
End point: recurrence of
AF Randomized
- Amiodarone (41 % recurrence)
- Amio + losartan (19% recurrence)
- Amio + perindopril (24 % rec.)
Yuehui et al. EHJ 2006;27:1841
ACE inhibition reduces atrial fibrosis in a
heart failure model
Control
5 Weeks
5 Weeks
+Enalapril
Li, Nattel, et al Circulation. 2001; 104: 2608
Role of ACEI and ARB’s in prevention of AF
• 56,308 patients (11 studies)
• Overall RR reduction of 28%
• Benefit is similar for ACEI or
ARBs
• RR reduction 44% in HF
Healey J, Baranchuk A, et al JACC 2005;45:1832
Prevention of AF - Statins
Recurrence after cardioversion of lone persistent AF
Antiinflammatory effect ? / Antioxidant effect ? / Antiarrhythmic effect ?
Siu et al. Am J Cardiol 2003; 92:1343 // Shiroshita-Takeshita et al. Circulation. 2004;110:2313-2319.
Rate vs Rhythm control
Rhythm Control
Rate Control
• Improve symptoms
• Improve symptoms
• Improve functional capacity
• Avoid side effects of AAD
• Lower risk of stroke
• Avoid pro-arrhythmia
• Avoid anticoagulation
•Improve survival
Rate vs Rhythm control
Vidaillet et al. Curr Opin Cardiol 20:15 // Testa et al. EHJ. 2005
AFFIRM
• 4060 patients
• No survival benefit (23.8% vs 21.3%)
• 23 % Prior HF
• Mean EF 55%
• Normal EF 74 %
NEJM 2002;347:1825
AFFIRM
NYHA
6’ walk
- SR improved survival
- AAD increased (non-cardiac) mortality
- Improved FC
JACC 2005;46:1891 / NEJM 2002;347:1825
RACE
Sub-study HF
• Rate control is not inferior to
rhythm
• If SR is maintained prognosis
may improve (more CV death,
HF hospitalizations and
Bleeding)
Hagens et al. Am Heart J 2005;149:1106
DIAMOND
• 506 pts with LV dysfunction
Survival according to rhythm
• Randomized to Dofetilide or Placebo
• No effect on mortality
• Effect of SR on mortality RR 0.44 (0.30-0.64)
Survival according to Rx
Pedersen et al. Circulation 2001;104:292
Management of AF in HR
SAFE T (persistent AF)
CTAF
Amiodarone has proven to be
safe in HF and CAD patients
NEJM 2000;342:913 / NEJM 2005;352:18
Management of AF in HR
Fuster, V. et al. Circulation 2006;114:e257-e354
Management of AF in HR
In HF patchy fibrosis
tends to accumulate at or
near PV ostia
Jaliffe et al. HRS 2007
AF ablation
AF ablation
RSPV
Management of AF in HF
• 58 pts
• HF and LVEF <45%
• FU= 12±7 m
• SR in 69 % at 12 months
• LVEF improved 21±13 %
• Improved exercise capacity,
symptoms, and QOL
NEJM 2004:351;23
Relation between AF and HF
Ablation
Neurohormonal/
Anti-inflammatory
Management of AF and HF
NYHA II-IV and EF < 35%
NYHA I and HF hosp or EF <25%
Management of AF in HR
Tachycardia Induced Cardiomyopathy
- Cardiomyopathy can be caused by any tachycardia (>110 bpm)
that occurs as little as 10-15% of day
- Severity related to rate and duration of  HR
- Maximal improvement after rate control may require up to 8
months
- After improvement susceptibility to rapid deterioration remains if
tachycardia recurs
Olshansky et al Circulation 2004 Fenelon et al PACE 1996; 19:95-106
Shinbane J et al. JACC 1997; 29: 709-715
Management of AF in HR
AV junction ablation and
Pacemaker Implantation
Advantages:
 Rate control without drugs
 Regularizes ventricular rate
Disadvantages
 Requires permanent pacemaker
 Fibrillation continues
 Risk of torsade de pointes
 Risk of hemodynamic deterioration (RV pacing)
Ozcan et al. NEJM 2001;344:1043
Management of AF in HF
Favor rhythm control




First or infrequent episodes of persistent AF
Significant symptoms in AF
Difficult rate control
Contraindication to long term warfarin
Favor rate control
 Asymptomatic in atrial fibrillation
 Contraindication to amiodarone
Antithrombotic Therapy
Risk of stroke 6% / y (5 - 6 fold increase)
Warfarin (INR 2.0 - 2.6):




62% reduction (CI 48% - 72%)
37 NNT to prevent 1 stroke
major hemorrhage: 0.6% / yr
20% discontinue anticoagulation
Aspirin (25 mg - 1300 mg/day)
 22% reduction (2% - 38%)
Hart et al. Ann Intern Med 1999;131:492
Antithrombotic Therapy
CHADS²
CHADS
Stroke rate
Score 1
2.8 %/y
Score 2
4.0 %/y
Score 3
5.9 %/y
Score 4
8.5 %/y
• Diabetes
Score 5
12.5 %/y
• Previos stroke (2 points)
Score 6
18.2 %/y
• Congestive HF
• Hypertension
• Age >75
Gage et al. JAMA 2001;285:2864
Summary
• AF and HF are not only clinically associated but are
physiopatologically inter-related
• AF seems to be a prognostic indicator (certainly recent onset AF)
irrespective of LV performance.
• Consequently prevention of AF should carry a better prognosis
• Although no benefit of rhythm vs rate control has been shown.
Data suggest that certain subgroup of patients will benefit from SR
• Irrespective of management strategy, antithrombotic Rx is
warranted
Conclusion
“I have been poor and I have
been rich. Rich is better.”
Attributed to Sophie Tucker