La gestione della fibrillazione atriale nel paziente con insufficienza cardiaca:

quando conservativi, quando aggressivi

Dipartimento di Cardiologia e Unita’ ScompensoPOLICLINICO DI MONZA, Monza

Andrea Mortara

Incontro con gli Esperti, Milano Settembre 2007

Wattigney, W. A. et al. Circulation 2003;108:711-716

Age-specific prevalence (per 10 000 population) of hospitalizations for atrial fib among adults age 35 yrs or

older by year, 1985 to 1999

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

Atrial fibrillation is increasing

FA sta aumentando negli anniFA e’ relata all’eta’ anche nello SC

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

Development of AF was associated with increased mortality: hazard ratio of 1.6 (95% CI, 1.2 to 2.1) in men and 2.7 (95% CI, 2.0 to 3.6) in

women.

Unadjusted cumulative incidence of first AF after Heart Failure - Framingham Study

20% of patients with heart failure develop AF within 4 years

CHF FA 54 per mille/persone/anno

FA CHF 33 per mille/persone/anno

Development of AF is associated with Clinical deterioration in Heart Failure

(Pozzoli et al JACC 1999)

• Prospective follow-up of 344 patients with CHF and sinus rhythm for 19 ± 12 months.

• 28 patients developed AF which became permanent in 18 pts• When AF occurred

– NYHA class worsened (from 2.4 ± 0.5 to 2.9 ± 0.6, p = 0.0001), – peak exercise O2 consumption declined (from 16 ± 5 to 11 ± 5 ml/kg per min,

p = 0.002), – cardiac index decreased (from 2.2 ± 0.4 to 1.8 ± 0.4, p = 0.0008), – mitral and tricuspid regurgitation increased

• thromboembolism occurred in 3 of the 18 patients with AF. • 9 of 18 patients died after AF • occurrence of AF was a predictor of major cardiac events.

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

Atrial Fibrillation is Associated with increased Mortality in Heart Failure

Dries et al SOLVD JACC 1998

RR 1.34 (1.11 - 1.61) adjusted for severity, medication

Atrial Fib Sinus pn 419 6098

Mortality 34% 23% <0.0001

Heart Failure Death 17% 9% <0.0001

Arrhythmic Death 7% 6% NS

The DIG Investigators. Chest. 2000;118:914-922.

From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF.

Atrial Fibrillation and risk of eventsin the CHARM Trial

(JACC 2006)

Pedersen OD Diamond Study Group, Circulation 2001

Atrial Fibrillation and Stroke: Meta-AnalysisHart et al, Ann Intern Med 1999; 131:492

• Risk of stroke 6% per yr (5 - 6 fold increase)• Warfarin (INR 2.0 - 2.6):

– 62% reduction (CI 48% - 72%) – N° needed to treat to prevent 1 stroke: 37 – intracranial hemorrhage: 0.3% / yr– major hemorrhage: 0.6% / yr– 20% of patients discontinue anticoagulation

• Aspirin (25 mg - 1300 mg/day)– 22% reduction (2% - 38%)

Stroke and cardiovascular conditionFramingham study(Wolf, 1991)

The elderly are particularly vulnerable to stroke when atrial fibrillation is present.

Atrial fibrillation In Dogs with Rapid Ventricular Pacing-Induced HF

(Stambler et al JCE 2003;14:499)

• CHF induced by 3 wks of rapid ventricular pacing– Inducible focal atrial tachycardias

consistent with triggerred automaticity associated with Ca+2 overload

– Atrial fibrosis– Prolongation of atrial action potential

duration

Dynamic Nature of Atrial Fibrillation Substrate During Development and Reversal of Heart Failure in Dogs

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

Masson trichrome-stained transverse LA sections from 1 representative dog per

group (original magnification x400)

Baseline

Heart failure induced by rapid ventricular pacing

Recovery from heart failure (5

weeks)

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.

*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

Adverse Hemodynamic Effects of AF

Irregular RR Intervals Impair Cardiac Performance

N=16

Patients who developed AF

Patients who remained in SR1,0

1,5

2,0

2,5

3,0Baseline

Finalevaluation

(in AF)

Last evaluation in SR

Finalevaluation

(in SR)

p=0.0008

p = 0.003

Car

dia

c in

dex

(l/m

in/m

2)

Changes of CI in patients Changes of CI in patients who did and did not develop AFwho did and did not develop AF

(Pozzoli et al, JACC 1998)(Pozzoli et al, JACC 1998)

The effects of rate and irregularity on sympathetic nerve activity in human

subjects. (Segerson NM et al Heart Rhythm 2007;4:20-6)

• It has been shown that atrial fibrillation is associated with an increase in sympathetic nerve activity (SNA) compared with sinus rhythm

• Greater degrees of irregularity cause greater sympathoexcitation and that the effects of irregular pacing on SNA are independent of the hemodynamic changes.

Affermazioni dalla letteratura

- Lo SCC e’ un fattore di rischio per sviluppare FA

- L’insorgenza di FA in pazienti con SCC e’ associato a deterioramento clinico ed emodinamico e ad una peggiore prognosi

- I dati danno percio’ una forte motivazione a prevenire e a trattare la FA nello SCC

“….. You will realize that blood gets into the ventricle not through any pull exerted by the distended heart but through the driving force exerted by the beats of auricles ..”

W. Harvey 1628

Ablazione della Fibrillazione Atrialenello Scompenso Cardiaco

R. superior pulmonary vein

R. inferior pulmonary vein

Coronary sinus

L. inferior pulmonary vein

L. atrium

L. superior pulmonary vein

L. auricle

L. pulmonary artery

R. pulmonary artery

LEFT ATRIUM Posterior basal view

Left Atrium, Posterior WallLeft Atrium, Posterior WallVariable Anatomy (Common)

Left Atrium, Posterior WallLeft Atrium, Posterior Wall

Asirvatham and Friedman.

From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF. 2005.

Modificata da D Parker circulation 2000

Relativa importanza del trigger Relativa importanza del trigger verso substratoverso substrato

Left Atrium, Posterior WallLeft Atrium, Posterior WallPulmonary Vein Isolation

Ablazione della FAAblazione della FAApproccio Circonferenziale

Combined Modality ImagingCombined Modality Imaging

1. Fluoroscopy (biplane, for rapid 3-D estimates)

2. High resolution gated CT or MRI

3. 3-D electroanatomic mapping

4. Intracardiac echo

In the future:

Multi-modality image co-registration combining

real-time anatomy and function…

Cu

rre

nt

Ablazione della Fibrillazione Atriale- Tecniche -

Left Atrium (LA) andPulmonary Vein Anatomy

3-D CT Reconstruction (Extreme PA Cranial View)

LA Roof

Esophagus

Left PVs

Right PVs

LA Appendage

• 58 consecutive patients with heart failure and LVEF <45%

• 58 control patients without CHF undergoing AF ablation matched for age, sex

• After 12±7 months, 78% of CHF pts vs 84% of controls remained in sinus rhythm (P=0.34) (69 % and 71% without antiarrhythmic drugs

• CHF pts had improvement in:– LV ejection fraction 21±13 %– LV diastolic diameter 6±6 mm – LV systolic diameter 8±7 mm– exercise capacity, symptoms, and and QoL– LV EF improved even if rate control before ablation

was judged adequate

Catheter Ablation for Atrial Fibrillation in Heart Failure

(Hsu LF et al New England J Med 2004)

Quando il controllo del Ritmonello Scompenso Cardiaco?

• Fattori favorevoli al controllo del Ritmo

– Primo o infrequenti episodi di FA persistente– FA asintomatica anche permanente, se mai eseguito un

tentativo di ripristino RS– FA sintomatica– Difficolta’ di controllo della frequenza– Controindicazioni a TAO

• Fattori favorevoli al controllo della Frequenza

– Eta’ biologica avanzata– Controindicazione all’amiodarone– Inefficace/i CVE

Medical Treatment (low estimate)

Medical Treatment (high estimate)

Catheter Ablation (low estimate)

Catheter Ablation (mean estimate)

Catheter Ablation (high estimate)

Cumulative Costsof Atrial Fibrillation Procedure in Ontario

Registro CanadeseY. Khaykin, J Cardiovasc Electrophysiol 2006

Costs equalized at 3.2-8.4 yrs of follow-up

Effetti Collateralidella Ablazione della FA

(6% delle procedure)

1. Stenosi della vena polmonare(Non e’ piu’ importante dopo il cambiamento della tecnica)

2. Tromboembolismi e Stroke(0-5%. TAO adeguata a ridotto il problema)

3. Fistola Atrio-Esofagea(rara, ma molto grave, dipende da estensione ablazione)

4. Flutter Atriale

5. Complicanze legate al cateterismo

• Vantaggi: – Adeguato controllo del ritmo senza farmaci– Regolarizzata la frequenza cardiaca

• Svantaggi:– Richiede impianto del PM (ma e’ + ICD) – FA continua: necessaria TAO– Rischio di Torsioni di Punta dopo ablazione AV– Rischio di deterioramento se stimolato da Vdx (Biv.)

Ablazione del Nodo AV e Impianto di PM Biv.+ICD

GN Kay et al Ablate and Pace J Intervent Card Electrophy 1998Brignole et al Circulation 1998Geelen P, et al. VF and sudden death after AVJ ablation. PACE 1997;20:343–8.Jordaens L, et al. Sudden death and long term survival . Eur J Card EP 1993;21:102–9.Gasparini M, et al. Long-term follow-up after AV ablation…PACE 2000;23:1925–9.Ozcan C, et al. Long-term survival …. . NEJM 2001;344: 1043–51.

Conservativi Aggressivi

HF+FA

1° Tentativo di CVE, Shock bifasico(TAO, tiroide a posto, PA controllata, terapia beta-bloccante)

2° Tentativo di CVE, Shock bifasico(dopo avere iniziato amiodarone)

ControlloDella Frequenza

TentativoDi ablazione

HF+FA

ControlloDella Frequenza

TentativoDi ablazione

1° Tentativo di ablazioneTecnica CARTO

Cardioversione Elettrica

2° Tentativo di ablazioneTecnica CARTO

FA

Digitale/amiodaroneOltre a B-bloccante

Valutazione in basalee durante sforzo

Monitorare l’efficaciadella terapia

nel controllare la frequenza

??

HF+FA

Impianto di ICDPM Biventricolare

AblazioneNodo AV

Digitale/amiodaroneOltre a B-bloccante

Valutazione in basalee durante sforzo

Insufficientecontrollo

Conservativi Aggressivi

Riduzione progressivadella frequenza di stimolazione

X

STUDI IN CORSO

AF-CHF = Controllo del Ritmo vs Frequenza

AVERT-HF = Ablazione nodo AV e BIV Pacing

CABANA = Ablazione AF superiore a terapia convenzionale