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

20% of patients with HF develop AF within 4 years 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

Class I – II Class III - IV Prevalence % Patients with Atrial Fibrillation prevalence increases with severity of heart failure Class I – II Class III - IV

Relation between AF and HF

Atrial Fibrillation Substrate Triggers

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 Paroxysmal AF Electrophysiologic Persistent AF ectopic foci Paroxysmal AF Electrophysiologic Remodeling Chronic Substrate fibrosis Persistent AF Permanent AF Stambler et al JCE 2003;14:499 Li, Nattel et al. Circulation. 1999;100:87-95

AF – Hemodynamic Effects Cardiac Output (L/Min) Cardiac Output (L/Min) NSR AF VVI VVI VVT 60 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 100 200 20 60 120 180 Nonfailing Failing Heart Rate (beats / min) % change in Force Mulieri Circulation 1992;

Effects of AF in HF Development of AF (28 pts): 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 % 13 % 19 % No AF Previous AF New onset AF Rivero-Ayerza et al. submitted EHS-HF EHS-HF

Independent predictors of hospital mortality Multiple logistic regression analysis Less likely to die More likely to die New Onset AF 1.5 (1.1-2.0) Previous AF Age Male Gender Rapid AF LA Dilatation EF  50% ACS VHD Renal Failure Stroke Elevated BP 0.1 1 10 OR (95%CI) Rivero-Ayerza et al. submitted EHS-HF

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 Prevention of AF would be ideal 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 functional capacity Lower risk of stroke Avoid anticoagulation Improve survival Improve symptoms Avoid side effects of AAD Avoid pro-arrhythmia

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 Survival according to rhythm Survival according to Rx 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 rhythm Survival according to Rx Pedersen et al. Circulation 2001;104:292

Amiodarone has proven to be safe in HF and CAD patients 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

AV junction ablation and Pacemaker Implantation 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 Score 5 12.5 %/y Score 6 18.2 %/y Congestive HF Hypertension Age >75 Diabetes Previos stroke (2 points) 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

“I have been poor and I have been rich. Rich is better.” Conclusion “I have been poor and I have been rich. Rich is better.” Attributed to Sophie Tucker