Management of Atrial Fibrillation in Heart Failure Maximo Rivero-Ayerza M.D. Clinical...

Management of Atrial Fibrillation in Heart FailureManagement of Atrial Fibrillation in Heart Failure

Maximo Rivero-Ayerza M.D.

Clinical Electrophysiology

Ziekenhuis Oost Limburg, Genk

Objectives Objectives

• Assess the relation between AF and HF

• Try to establish the optimal treatment strategy

Wang, T. J. et al. Circulation 2003;107:2920-2925

↑ Mortality in AF: - Men HR 1.6- Women HR 2.7

Unadjusted cumulative incidence of first AF after Heart Failure - Framingham

Study

20% of patients with HF develop AF within 4 years

PrevalencePrevalence

Wattigneyet al. Circulation 2003;108:711-716

Concomitant HF: 13 % age 35 – 64 yrs 21% age > 65 yrs


0

0.1

0.2

0.3

0.4

0.5

0.6

% Patients with Atrial Fibrillation

prevalence increases with severity of heart failure

Class I – II Class III - IV


Relation between AF and HFRelation between AF and HF

Triggers

Atrial Fibrillation

Substrate

Shinagawa, K. et al. Circulation 2002;105:2672-2678

AF – Atrial remodelingAF – 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.

Kalifa et al. Circulation. 2003;108:668.

5 cm H2O 18 cm H2O

Increases in intra-atrial Increases in intra-atrial pressure increases the pressure increases the rate of the dominant rate of the dominant frequency at the level of frequency at the level of the PV junction compared the PV junction compared to LA free wallto LA free wall

Effect of intra-atrial pressure on AF Effect of intra-atrial pressure on AF

Kalifa et al. Circulation. 2003;108:668.

Effect of intra-atrial pressure on AF Effect of intra-atrial pressure on AF

Increases in intra-atrial Increases in intra-atrial pressure increases the pressure increases the number of waves (rotors) number of waves (rotors) emanating from the PVsemanating from the PVs

Paroxysmal AF

Persistent AF

Permanent AF

Triggersectopic foci

ElectrophysiologicRemodeling

Chronic Substratefibrosis

Stambler et al JCE 2003;14:499Li, Nattel et al. Circulation. 1999;100:87-95

Types of AF

*p < 0.01

NSR AF VVI VVI VVT 60 AVG

VVI -AVG VVT

C

ard

iac

Ou

tpu

t (L

/Min

)

C

ard

iac

Ou

tpu

t (L

/Min

)

Clark DM. JACC 1997; 30:1039-45

N=16

AF – Hemodynamic EffectsAF – Hemodynamic Effects

0

100

200

20 60 120 180

Nonfailing Failing

Heart Rate (beats / min)

% c

han

ge

in F

orc

e

Effects of AF in HFEffects of AF in HF

Mulieri Circulation 1992;

Rapid heart rates depress contractility: abnormal force - frequency relationship in heart failure

Pozolli et al. JACC 1998;31(1):197-204.

Effects of AF in HFEffects of AF in HF

Development of AF (28 pts):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)

344 HF pts FU= 19± 12 months

Prognostic significanse of AF 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


COMMET

N= 3029 pts (20% with AF)

Age= 62 y

Baseline AF RR=1.29 (univariate)

Baseline AF predictive of HF hosp.

New Onset AFNew Onset AF RR=1.90 (multivariate) RR=1.90 (multivariate)

Eur Heart J 2005;26:1303


DIG

N= 6800 pts (11% SVT)

Age= 63 y

RR= 2.45

CHEST 2000;118:914

Prognostic significanse of AF EpidemiologicalPrognostic significanse of AF Epidemiological

Wang TJ. Et al Circulation. 2003;107:2920

• 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.

EHS-HFEHS-HF

In-hospital mortality 12 week mortality

7%7% 7%7% 12 %12 % 13 %13 %

P < 0.001P < 0.001 P < 0.001P < 0.001

No AF Previous AF New onset AF

1313 % % 19 %19 %

Rivero-Ayerza et al. submitted

EuroHeart Failure - Mortality EuroHeart Failure - Mortality

EHS-HF

Less likely to die More likely to die

1.5 (1.1-2.0)1.5 (1.1-2.0)

0.1 1 10

Elevated BPStroke

Renal FailureVHDACS 50%EF

LA DilatationRapid AF

Male GenderAge

Previous AFNew Onset AF

OR (95%CI)

Independent predictors of hospital mortality Independent predictors of hospital mortality

Multiple logistic regression analysisMultiple logistic regression analysis

Rivero-Ayerza et al. submitted

AF and HF AF and HF

• AF and HF tend to AF and HF tend to coexistcoexist and share and share predisposingpredisposing factors factors

• One may directly One may directly predisposepredispose to the other to the other

• The The combinationcombination of both is believed to carry a of both is believed to carry a worseworse

prognosisprognosis then either alone. then either alone.

• In the setting of HF In the setting of HF onset of AFonset of AF seems to be a stronger seems to be a stronger

predictor of predictor of adverse outcome adverse outcome irrespective of LV function

SummarySummary

Management of AF in HF Management of AF in HF

1.1. PreventionPrevention of AF would be ideal of AF would be ideal

2.2. Avoiding Avoiding hemodynamichemodynamic deteriorationdeterioration

and and improvingimproving symptomssymptoms

3. Preventing 3. Preventing strokestroke

ObjectivesObjectives

177 pts parox AF

End point: recurrence of

AF Randomized

- Amiodarone (41 % recurrence)

- Amio + losartan (19% recurrence)

- Amio + perindopril (24 % rec.)

Role of ACEI and ARB’s in prevention of AFRole of ACEI and ARB’s in prevention of AF

Yuehui et al. EHJ 2006;27:1841

Control

5 Weeks

5 Weeks +Enalapril

Li, Nattel, et al Circulation. 2001; 104: 2608

ACE inhibition reduces atrial fibrosis in a ACE inhibition reduces atrial fibrosis in a heart failure modelheart failure model

Healey J, Baranchuk A, et al JACC 2005;45:1832

Role of ACEI and ARB’s in prevention of AFRole 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

Siu et al. Am J Cardiol 2003; 92:1343 // Shiroshita-Takeshita et al. Circulation. 2004;110:2313-2319.

Prevention of AF - StatinsPrevention of AF - Statins

Recurrence after cardioversion of lone persistent AFRecurrence after cardioversion of lone persistent AF

Antiinflammatory effect ? / Antioxidant effect ? / Antiarrhythmic effect ?

Rate vs Rhythm controlRate vs Rhythm control

Rhythm ControlRhythm Control Rate ControlRate Control

• Improve symptoms

• Improve functional capacity

• Lower risk of stroke

• Avoid anticoagulation

•Improve survival

• Improve symptoms

• Avoid side effects of AAD

• Avoid pro-arrhythmia

Rate vs Rhythm controlRate vs Rhythm control

Vidaillet et al. Curr Opin Cardiol 20:15 // Testa et al. EHJ. 2005

AFFIRMAFFIRM

NEJM 2002;347:1825

• 4060 patients • No survival benefit (23.8% vs 21.3%) • 23 % Prior HF • Mean EF 55%• Normal EF 74 %

AFFIRMAFFIRM

JACC 2005;46:1891 / NEJM 2002;347:1825

- SR improved survival

- AAD increased (non-cardiac) mortality

- Improved FC

NYHA

6’ walk

RACERACE

Hagens et al. Am Heart J 2005;149:1106

Sub-study HFSub-study HF

• Rate control is not inferior to rhythm

• If SR is maintained prognosis may improve (more CV death, HF hospitalizations and Bleeding)

DIAMONDDIAMOND

Pedersen et al. Circulation 2001;104:292

• 506 pts with LV dysfunction

• 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

Survival according to rhythm

Management of AF in HRManagement of AF in HR

NEJM 2000;342:913 / NEJM 2005;352:18

SAFE T (persistent AF) CTAF

Amiodarone has proven to be safe in HF and CAD patients


Fuster, V. et al. Circulation 2006;114:e257-e354


Jaliffe et al. HRS 2007

In HF patchy fibrosis tends to accumulate at or near PV ostia

AF ablationAF ablation

RSPV

AF ablationAF ablation

Management of AF in HFManagement of AF in HF

NEJM 2004:351;23

• 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

Relation between AF and HFRelation between AF and HF

Ablation

Neurohormonal/Anti-inflammatory

Management of AF and HFManagement of AF and HF

NYHA II-IV and EF < 35%

NYHA I and HF hosp or EF <25%

- 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

Tachycardia Induced CardiomyopathyTachycardia Induced Cardiomyopathy



Ozcan et al. NEJM 2001;344:1043

Advantages:Advantages: Rate control without drugs Regularizes ventricular rate

DisadvantagesDisadvantages Requires permanent pacemaker Fibrillation continues Risk of torsade de pointes Risk of hemodynamic deterioration (RV pacing)

AV junction ablation AV junction ablation and Pacemaker and Pacemaker

ImplantationImplantation

Favor rhythm controlFavor rhythm control

First or infrequent episodes of persistent AF Significant symptoms in AF Difficult rate control Contraindication to long term warfarin

Favor rate controlFavor rate control

Asymptomatic in atrial fibrillation Contraindication to amiodarone

Management of AF in HFManagement of AF in HF

Risk of stroke 6% / y (5 - 6 fold increase)

Warfarin (INR 2.0 - 2.6):Warfarin (INR 2.0 - 2.6):

62% reduction62% reduction (CI 48% - 72%) 37 NNT to prevent 1 stroke major hemorrhage: 0.6% / yr 20% discontinue anticoagulation

Aspirin (25 mg - 1300 mg/day)Aspirin (25 mg - 1300 mg/day)

22% reduction (2% - 38%)

Antithrombotic TherapyAntithrombotic Therapy

Hart et al. Ann Intern Med 1999;131:492

Antithrombotic TherapyAntithrombotic Therapy

CHADSCHADS²²

• Congestive HF

• Hypertension

• Age >75

• Diabetes

• Previos stroke (2 points)

Score 1 2.8 %/y

Score 2 4.0 %/y

Score 3 5.9 %/y

Score 4 8.5 %/y

Score 5 12.5 %/y

Score 6 18.2 %/y

Stroke rateCHADS

Gage et al. JAMA 2001;285:2864

SummarySummary

• 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

ConclusionConclusion

“I have been poor and I have been rich. Rich is better.”

Attributed to Sophie Tucker

Management of Atrial Fibrillation in Heart Failure Maximo Rivero-Ayerza M.D. Clinical...

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