41° Convegno CARDIOLOGIA 2007Milano, 17/21 Settembre 2007

LA GESTIONE DELLA FIBRILLAZIONE ATRIALE

NEL PAZIENTE CON INSUFFICIENZA CARDIACA:

QUANDO CONSERVATIVI,QUANDO AGGRESSIVI.

G. Di TanoU.O. Cardiologia

Az. Osped. Papardo, Messina

INCONTRI CON GLI ESPERTI INCONTRI CON GLI ESPERTI

Wang TJ et al. Circulation 2003;107:2920

Unadjusted cumulative incidence

of first CHF in individuals with AF

Unadjusted cumulative incidence

of first AF in individuals with CHF

ATRIAL FIBRILLATION : PREVALENCE INCREASE WITH SEVERITY OF

HEART FAILURE

Camm AJ et al. Dialog Cardiovasc Med, 2003

Heart Failure

Atrial Remodeling

Atrial Fibrillation

LA pressureAngiotensin IIAldosterone

Atrial Fibrosis

Stretch sympathetic tone

Ectopic activity

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

Heart Failure

Atrial Remodeling

Atrial Fibrillation

LA pressureAngiotensin IIAldosterone

Atrial Fibrosis

Stretch sympathetic tone

Ectopic activity

Loss of atrial contraction

Irregular R-R Intervals

RapidRate

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

in heart failure

0

100

200

20 60 120 180

Nonfailing Failing

Heart Rate (beats / min)

% c

han

ge

in F

orc

e

Pieske Circ Res 1999; Gwathmey JCI 1990; Mulieri Circulation 1992;Heerdt PM, Circulation. 2000;102:2713-9.

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 upto 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

Atrial Fibrillation and Tachycardia Induced

Cardiomyopathy

APPROCCIO CONSERVATIVO...

APPROCCIO AGGRESSIVO…

GESTIONEGestione della Fibrillazione Atriale nello Scompenso Cardiaco

TERAPIAOTTIMIZZATA

DELLO SCOMPENSO

Prevention of Atrial Fib With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers:

A Meta-Analysis Healey, et al JACC 2005;45:1832

• 11 studies with 56,308 patients• Overall, ACEIs and ARBs reduced the relative risk of

AF by 28%• Benefit is similar for ACE-inhibitors and AII blockers• Reduction in AF was greatest in patients with heart

failure (relative risk reduction 44%, p = 0.007). • There appears to be a large effect after

cardioversion (48% RRR), but the confidence limits are wide (95% CI 21% to 65%)

Atrial Fibrillation in Patients with Heart Failure: Management

• Rate control

• Anticoagulation

• Rhythm control = restore sinus rhythm or

• Rate control = remain in fibrillation

Atrial Fibrillation: Rate Control

• digoxin – poor efficacy but well tolerated

• beta - adrenergic blockers• calcium channel blockers – effective but

negative inotropic effects– verapamil, diltiazem

• amiodarone – effective but potential major toxicity

{

Atrial Fibrillation + Heart Failure

Rate Control

Rhythm Control(restore and maintain

sinus rhythm)

??Avoidance

antiarrhythmicdrugs…

Reduced need for repeated CVE

Improved cardiac function and symptoms

Improved QL

Prevention TE

Atrial Fibrillation in Heart Failure

• Patients with AF have increased mortality compared to SR patients

• Patients who convert to SR have lower mortality than those who remain in AF

Should patients with heart failure and AF be converted and maintained in sinus rhythm?

Wang Circ 2003;107:2920; Middlekauff Circ 1991; 84: 40Dries JACC. 1998; 32: 695; Deedwania Circ 1998; 98: 2574; Pozzoli JACC 1998; 32: 197; Torp-Pedersen NEJM 1999; 341: 857

Rate Control

Rhythm Control“ If you were born in sinus rhythm,

you should probably try to remain so”.

AFFIRMPIAFRACESTAF

AFFIRMA Comparison of Rate Control and Rhythm Control in

Patients with Atrial FibrillationNEJM 347:1825, 2002

4060 patients (age 70 yrs) Mortality at 5 yrs (p = 0.06):

rhythm control 23.8% vs 21.3% rate control

Rhythm control (RS only in 63%) increased hospitalizations increased exposure to drug adverse effects did not reduce strokes did not improve functional capacity or quality of life

Most strokes occurred after warfarin had been stopped or was subtherapeutic

AFFIRM was not a Heart Failure TrialPrior CHF: 23.1%

Mean EF: 55%

“Normal” LV ejection fraction in 74%

- Presence of RS carried a small, but statically significant, improvement in NYHA functional class at follow-up.

Chung MK et al, J Am Coll Cardiol 2005;46:1891

- 939 HF pts: no benefit of a strategy of rhythm control.

Is rhythm control superior to rate control in patients with atrial fibrillation and congestive heart failure?

Al-Khatib SM et al., Am J Cardiol 2004;94:797

In 1,009 patients with AF and congestive heart failure, the 1-year mortality rate was identical (both 21%) and at 2-year mortality rate was 31% in patients treated with rate control (n = 505) versus 29% in patients treated with rhythm control (n = 504). After adjusting for differences in baseline characteristics and medications, no significant difference in mortality was found between the 2 groups (p=.79)

Am Heart J 2005:149;1106

Motivi della mancata efficacia della strategia

Rhythm control

Effetto deleterio degli antiarimici (minor efficacia, azione proaritmica - aritmie ventricolari, aumentato FCV durante AF, bradiaritmie - , inotropi negativi, tossicità)

Interazioni farmacologiche Conversione di episodi di FA sintomatici in

episodi “silenti” … Sospensione anticipata TAO

Class I antiarrhythmic drugs increase mortality in patients with heart failure and AF - (post-hoc analysis) SPAF, JACC 1992

Rate Control vs Rhythm Control

Favor rate control Asymptomatic, old, pts in atrial fibrillation Contraindication to amiodarone

Favor attempts to maintain sinus rhythm First or infrequent episodes of persistent AF Significant symptoms in AF Difficult rate control Contraindication to long term warfarin

Class I anti-arrhythmic drugs should be avoided as they may provoke fatal ventricular arrhythmias, have an adverse hemodynamic effect and reduce survival in heart failureLevel of evidence B, class III

Background Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects.

Methods In two identical multicenter, double-blind, randomized trials, one conducted in Europe and one conducted in the United States, Canada, Australia, South Africa, and Argentina , we evaluated the efficacy of dronedarone, with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo. Rhythm was monitored transtelephonically on days 2, 3, and 5; at 3, 5, 7, and 10 months; during recurrence of arrhythmia; and at nine scheduled visits during a 12-month period. The primary end point was the time to the first recurrence of atrial fibrillation or flutter.

Results In the European trial, the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group (P=0.01). The corresponding durations in the non-European trial were 59 and 158 days (P=0.002). At the recurrence of arrhythmia in the European trial, the mean (±SD) ventricular rate was 117.5±29.1 beats per minute in the placebo group and 102.3±24.7 beats per minute in the dronedarone group (P<0.001); the corresponding

rates in the non-European trial were 116.6±31.9 and 104.6±27.1 beats per minute (P<0.001). Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group.

Conclusions Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia.

18% dei pz era in classe NYHA I - II

III - IV classe esclusi

ANDROMEDA:Trial in pz con SC

interrotto per > rischio di mortalità nei

trattati

SHOCK BIFASICO (energie minori; a 150 J successo >90%)

OTTIMIZZAZIONE DELLA CARDIOVERSIONE ELETTRICA ESTERNA

PLACCHE ANTERO-POSTERIORE

AMIODARONE 400 mg/die, 1 mese prima e 1-2 mesi dopo CVE: aumenta percentuale di RS e recidive FA a 1m

CONTROINDICAZIONI: No TAO Temporanee: Trombosi atriale Terapia digitalica Ipertiroidismo…

IPERTIROIDISMO SUB-CLINICO E FIBRILLAZIONE ATRIALE

• Bassa concentrazione di TSH (-soppresso-, < 0.01 µIU/ml) con normali livelli di FT3 e FT4 , in pazienti asintomatici.

• Prevalenza dell’11.8% tra gli anziani

(0.5% - 3.9% negli adulti)• Framingham (< 65 a): a 10 anni:

- FA nel 28% in pz con SCHyp

11% nei normali

Sawin CT, Thyroid 2002

Cosa mi aspetta al rientro…

Uomo, 57 anni, professionista, senza FR, CMD primitiva

• 01/04: insorgenza SC con FA ad elevata FCVm, BBSn, NYHA III;

ECO: FE 25%, ipoc glob; DTD 62mm; IM ++, IT+++, dilatazione biatriale.

• Terapia: diuretici, ace-i; digitale; TAO. Migliorato, - 8 Kg, BNP in calo

• 03/04: Ricovero: coronarie normali, biopsia (neg); ECO: FE 30%, IM +;

I T++, RS dopo CVE; profilassi con amiodarone ; inizia carvedilolo.

- Ipotensione sintomatica: sospende ace-i; passa a bisoprololo

- Progressiva stabilità. BNP 230

• 07/04: Ipertiroidismo iatrogeno. Sospende amiodarone. Resta in TAO

- ECO: FE 35%, DTD: 58mm; AS: 19cm2.

• 02/05: Stabile; NYHA 1-2; Ormoni tiroidei normali; ECO: FE 35-40%, TAO

•12/06: Recidiva FA. (cardiopalmo, dispnea lieve…) , BNP 373

• 01/07: CVE efficace (shock bifasico, 75J): RS. Terapia confernata…

• 06/07: Stabile; ECO: FE 38%,DTD 54mm, AS:42mm, AD:23cm2, IM+,

IT+; BNP 250.

• 07/07: Riscontro occasionale di recidiva FA (60 b/m); asintomatico, BNP =

• 08/07: Persiste FA (FVm: 58b/m); asintomatico; non dispnea da sforzo.

• 09/07: Astenia, dispnea da sforzo… .

Cosa fare ?