What Is the Outcome of Atrial Fibrillation Ablation in Patients with Left Ventricular Dysfunction?

with Left Ventricular Dysfunction?

L.-F. H

, P. S

, M. H

, F. S

, M. R

, Y. T

, T. R

, C. S

, M. H

, P. J

Introduction

Atrial fibrillation (AF) and congestive heart failure (CHF) are closely related conditions. While CHF promotes the development of AF, the presence of AF may exacerbate or, in some cases, cause left ventricular (LV) dysfunction, with symptoms of CHF as a consequence [1, 2]. In addition, each disease adversely affects the prognosis of the other [3, 4].

Cardiomyopathy due to rapid uncontrolled ventricular response has been implicated as the main mechanism by which AF results in LV dysfunction [5]. However, in the absence of a rapid ventricular rate during AF, LV dys- function can still occur as a result of impaired atrial contractile function, loss of atrioventricular synchrony, or an irregular ventricular rhythm [58].

Rhythm vs Rate Control for AF in Heart Failure

The most effective strategy to prevent or reverse LV dysfunction associated with AF is the restoration and maintenance of sinus rhythm. However, to achieve this with the use of antiarrhythmic drugs is extremely challenging, owing to the limited efficacy and potentially deleterious effects of these drugs [9]. This has led to renewed interest in rate control, stimulated by reports from large randomised studies, especially the Atrial Fibrillation Follow-up Investigation of Rhy thm Management (AFFIRM) and Rate Control versus Electrical Cardioversion (RACE) trials, suggesting a compara- ble outcome for strategies involving pharmacological rhythm or rate control

1

National Heart Centre, Singapore;

Hôpital Cardiologique du Haut-Lévêque, Bordeaux-

Pessac, France

[10-12]. However, recent evidence from these two studies not only confirmed the adverse prognostic effects of CHF, but also highlighted the potential ben- efits of sinus rhythm. In a recently reported substudy of the AFFIRM trial, restoration and maintenance of sinus rhythm was associated with a 47%

reduction in mortality risk, while the use of antiarrhythmic drugs and the presence of CHF significantly increased the risk of death by 49% and 57%, respectively [13]. In a separate substudy, the RACE investigators also demon- strated that, although pharmacological rate control could prevent deteriora- tion of LV function, restoration and maintenance of sinus rhythm were asso- ciated with improvement of LV function [14].

In patients with LV dysfunction, modest improvements in LV ejection fraction (LVEF) and fractional shortening can be achieved nonpharmacolog- ically using the clinically proven and effective ‘ablate and pace’ strategy [15 17]. However, while it provides effective ventricular rate control and rhythm regularisation, it does not restore atrial contraction or atrioventricular or interventricular synchrony. In addition, the benefit of rhythm regularisation can be negated by the adverse haemodynamic effects of right ventricular (RV) pacing, which is commonly used in such patients. The use of LV or biventricular pacing, associated with a more favourable haemodynamic pro- file, may avoid this problem, although present evidence is inconclusive [18, 19]. Finally, long-term pacemaker dependence is also an important consider- ation for this strategy.

Catheter Ablation of AF in Heart Failure

The advent of catheter ablation as an effective therapy for AF resistant to pharmacologic rhythm or rate control has provided a viable strategy to restore and maintain sinus rhythm without the use of antiarrhythmic drugs.

With current techniques and technology, long-term sinus rhythm can be restored in up to 90% of patients with paroxysmal AF, usually without the need for antiarrhythmic drugs [20]; however, ablation of permanent AF remains more difficult, often requiring extensive atrial ablation and multiple procedures.

Maintenance of Sinus Rhythm

Currently available results of patients with CHF who have undergone catheter ablation for AF are summarised in Table 1. A large proportion of these patients have permanent AF of significant duration (average of approx- imately 7 years) and other structural heart disease. In the two published studies, a significant number required multiple ablation procedures (27%

and 50%, respectively) [21, 22]. Nonetheless, catheter ablation has been

demonstrated to be feasible in these patients and is associated with a good success rate for sinus rhythm maintenance, ranging from 68% to 96%, mostly without use of antiarrhythmic drugs [21–25].

Table 1. Summar y o f res ul ts o f at rial fi b ril la tio n (AF) a bla tio n in p at ien ts w ith c o ngest iv e hear t f ail ur e (CHF) P at ien ts P er manen t Dura tio n o f R epea t Sin us P re-a bla tio n P ost-a bla tio n (n) AF AF (y ear s) abla tio n rh y thm LVEF (%) LVEF (%) Chen/N atale (C lev eland C linic) [21] 94 55 (56%) 6 ± 2 21 (22%) 90 (96%) 36 ± 7 41 ± 6 Hs u/J aïs/H aÏssag uer e (Bo rdea ux) [22] 58 53 (91%) 7 ± 4 29 (50%) 45 (78%) 35 ± 7 56 ± 13 P ap p o ne et al. (Milan) [23] 95 N A 6 ± 3 N A 77 (81%) 31 ± 9 44 ± 6 Cha/P ack er (M ay o C linic) [24] 19 7 (37%) 7 ± 5 N A 13 (68%) 34 ± 6 51 ± 7 Gen tles k /M ar chlin sk i (P enn sy lv ania) [25] 53 17 (32%) N A N A 48 (90%) 42 ± 8 57 ± 8 LVEF L ef t v en tr icular ejec ti o n f rac ti o n ,NA da ta no t a vaila ble

These results have also been achieved with an acceptable safety profile. In the two published studies, significant pulmonary vein (PV) stenosis was lim- ited to < 1%, cardiac tamponade ~2%, and stroke ~2% [21, 22], results com- parable to patients without CHF or structural heart disease [20]. An addi- tional complication in CHF was the development of pulmonary oedema dur- ing the procedure, observed in one patient in the study by Chen et al. [21], and in two of our patients. These patients were treated for their acute decompensation, and AF was successfully ablated in a subsequent procedure.

Symptoms and Quality of Life

In patients without CHF, catheter ablation of AF has been demonstrated to improve symptoms and quality of life [26]. Similarly, these findings have been observed in CHF patients. CHF symptoms improved by approximately one NYHA class after ablation (Hsu et al. [22], from 2.3 to 1.5; Pappone et al.

[23], from 2.8 to 1.6; and Cha et al. [24], from 2.3 to 1.5), while arrhythmia- related symptoms, as assessed by the Symptom Checklist-Frequency and Severity scores, also improved significantly [22]. Overall quality of life, assessed with the 36-item Short Form General Health Survey (SF-36) ques- tionnaire, also improved significantly in all scales [21-23]. Among our patients, the summary scores for the physical and mental components increased by an average of 24 and 21 points, respectively [22].

Left Ventricular Function

An improvement in LV function after ablation has been demonstrated in all five studies currently available (Table 1), with mean improvements in LVEF ranging from 5% to 21% [21-25]. Importantly, Gentlesk et al. demonstrated a

‘normalisation of LVEF’ to > 55% in 87% of patients in their series [25], while 72% of our patients demonstrated a ‘marked improvement of LVEF,’

defined as an increase of ≥ 20% or to ≥ 55% [22].

Concurrently, LV dilatation was reduced significantly. Among our

patients, LV end-systolic diameter was reduced by 6 ± 6 mm while end-sys-

tolic diameter was reduced by 8 ± 7 mm. Not surprisingly, recurrence of

arrhythmia despite the use of antiarrhythmic drugs negatively affected the

recovery of LVEF. However, LV function was still significantly improved in

four of 12 patients with recurrent AF, as ablation had converted permanent

AF to paroxysmal AF [22]. In addition, two of our three patients being con-

sidered for heart transplant improved sufficiently after ablation to merit

removal from the active transplant list.

Effect of Coexisting Heart Disease

The presence of concurrent structural heart disease (ischaemic, valvular, hypertensive, or hypertrophic cardiomyopathy) did not significantly affect the outcome of ablation. Among our patients, sinus rhythm was maintained in 73% of patients with structural heart disease (66% without antiarrhyth- mic therapy) compared to 81% (73% without drugs) in patients without coexisting heart disease. Similarly, LVEF improved significantly in these patients by 16 ± 14% [22]. These findings were also observed in the series by Chen et al. [21].

Effect of Ventricular Rate Control

Effective ventricular rate control in AF using pharmacological measures or the ‘ablate and pace’ strategy have been demonstrated to improve LV dys- function [5]. However, even in patients with adequate ventricular rate con- trol, restoration and maintenance of sinus rhythm after catheter ablation resulted in further improvement of LVEF. Among our patients, LVEF increased by 17 ± 15% in those with good pre-ablation rate control (defined as mean ventricular rate < 80 beats/min at rest) [22]. Similarly, among 17 patients with persistent/permanent AF in Gentlesk’s series, 10 had rate con- t rol < 90 b eats/min at rest [25], w hile most of the pat ients w ith persistent/permanent AF in Chen’s series were already well rate-controlled before ablation [21].

This finding could indicate that the degree of rate control was overesti- mated or, more likely, that the irregularity of the rhythm as well as the loss of atrial contractility and atrioventricular synchrony contributed to the LV dys- function. Thus, restoration of sinus rhythm should be expected to confer additional haemodynamic benefits compared with pharmacological rate control.

Implications

Though the individual studies are small, their results have been remarkably

consistent and challenge the notion that rate control is as good as rhythm

control, especially in patients with CHF. A recent study evaluating an aggres-

sive pharmacological rhythm-control strategy, utilising external or internal

cardioversion and treatment with amiodarone, demonstrated long-term ben-

efits in patients with advanced CHF [27]. Among 74 patients in this study,

sinus rhythm was maintained in 70% and 55% at 1 and 3 years, respectively.

LVEF was significantly improved, from 28 ± 7% at baseline to 38 ± 11%

and 35 ± 12% at 1 and 3 years, while NYHA class significantly improved from 2.7 to 2.1 and 2.0, respectively. In addition, three patients were removed from the active heart transplant list due to marked clinical improvement.

While these observations are striking, it should be noted that sinus rhythm was maintained with high-dose amiodarone. A further issue not addressed in present drug or catheter ablation studies is the mortality bene- fit of restoring and maintaining sinus rhythm in patients with CHF, although several randomised trials have alluded to improved survival among patients with CHF and AF who reverted to sinus rhythm [13]. Presently a large multi- centre study, the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial, is being conducted to evaluate whether the benefits of sinus rhythm in CHF patients are sufficiently great to offset the risks of antiarrhythmic drug therapy.

Conclusions

Present evidence indicates that patients with CHF and AF may benefit from restoration and maintenance of sinus rhythm, if it can be achieved without the adverse effects of treatment. Further improvements are needed to make catheter ablation of AF easier and safer, in order to increase its availability outside experienced centres [28]. Nonetheless, curative ablation offers the unique opportunity to maintain sinus rhythm without the use of potentially harmful antiarrhythmic drugs, resulting in significant improvements in car- diac function, symptoms and quality of life.

References

1. Stevenson WG, Stevenson LW (1999) Atrial fibrillation in heart failure. N Engl J Med 341:910–911

2. Ehrlich JR, Nattel S, Hohnloser SH (2002) Atrial fibrillation and congestive heart failure: specific considerations at the intersection of two common and important cardiac disease sets. J Cardiovasc Electrophysiol 13:399–405

3. Middlekauff HR, Stevenson WG, Stevenson LW (1991) Prognostic significance of atrial fibrillation in advanced heart failure: a study of 390 patients. Circulation 84:40–48

4. Wang TJ, Larson MG, Levy D et al (2003) Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality : the Framingham Heart Study. Circulation 107:2920–2925

5. Shinbane JS, Wood MA, Jensen DN et al (1997) Tachycardia-induced cardiomyo-

pathy : a review of animal models and clinical studies. J Am Coll Cardiol

29:709–715

6. Natale A, Zimerman L, Tomassoni G et al (1996) Impact on ventricular function and quality of life of transcatheter ablation of the atrioventricular junction in chronic atrial fibrillation with a normal ventricular response. Am J Cardiol 78:1431–1433

7. Clark DM, Plumb VJ, Epstein AE et al (1997) Hemodynamic effects of an irregular sequence of ventricular cycle lengths during atrial fibrillation. J Am Coll Cardiol 30:1039–1045

8. Daoud EG, Weiss R, Bahu M et al (1996) Effect of an irregular ventricular rhythm on cardiac output. Am J Cardiol 78:1433–1436

9. Falk RH (2001) Atrial fibrillation. N Engl J Med 344:1067–1078

10. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347:1825–1833

11. Van Gelder IC, Hagens VE, Bosker HA et al (2002) A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 347:1834–1840

12. Hohnloser SH, Kuck KH et al (2000) Rhythm or rate control in atrial fibrillation—

Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial.

Lancet 356:1789–1794

13. Corley SD, Epstein AE, DiMarco JP et al (2004) Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study. Circulation109:1509–1513

14. Hagens VE, Van Veldhuisen DJ, Kamp O et al (2005) Effect of rate and rhythm con- trol on left ventricular function and cardiac dimensions in patients with persistent atrial fibrillation: results from the Rate Control versus Electrical Cardioversion for persistent atrial fibrillation (RACE) study. Heart Rhythm 2:19–24

15. Wood MA, Brown-Mahoney C, Kay GN et al (2000) Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis. Circulation 101:1138–1144

16. Brignole M, Menozzi C, Gianfranchi L et al (1998) Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: a randomized controlled study. Circulation 98:953–960

17. Ozcan C, Jahangir A, Friedman PA et al (2003) Significant effects of atrioventricu- lar node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunc- tion. Am J Cardiol 92:33–37

18. Doshi R, Daoud E, Fellows C et al (2004) PAVE: the first prospective randomized study evaluating biventricular pacing after ablate and pace therapy. Presented at the American College of Cardiology Annual Scientific Session 2004, March 7–10, New Orleans, LA

19. Brignole M, Gammage M, Puggioni E et al on behalf of the Optimal Pacing Site (Opsite) Study Investigators (2005) Comparative assessment of right, left and biventricular pacing in patients with permanent atrial fibrillation. Eur Heart J:26:712–722

20. Cappato R, Calkins H, Chen SA et al (2005) Worldwide survey on the methods, effi- cacy and safety of catheter ablation for human atrial fibrillation. Circulation 111:1100–1115

21. Chen MS, Marrouche NF, Khaykin Y et al (2004) Pulmonary vein isolation for the

treatment of atrial fibrillation in patients with impaired systolic function. J Am

Coll Cardiol 43:1004–1009

22. Hsu LF, Jaïs P, Sanders P et al (2004) Catheter ablation for atrial fibrillation in con- gestive heart failure. N Engl J Med 351:2373–2383

23. Pappone C, Augello G, Vicedomini G et al (2003) Circumferential pulmonary vein ablation in patients with atrial fibrillation and associated systolic or diastolic heart failure. Eur Heart J 24:494 (abs)

24. Cha YM, Asirvatham SJ, Friedman PA et al (2004) Improvement in left ventricular function following radiofrequency catheter ablation of atrial fibrillation in patients with congestive heart failure. Heart Rhythm 1:S139 (abs)

25. Gentlesk P, Sauer WH, Zado ES et al (2004) Ablation of atrial fibrillation in patients with decreased ejection fraction: outcome and evidence for reversible cardiomyo- pathy. Heart Rhythm 1:S171-S172 (abs)

26. Pappone C, Rosanio S, Augello G et al (2003) Mortality, morbidity and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled, nonrandomized long-term study. J Am Coll Cardiol 42:185–197 27. De Ferrari GM, Petracci B, Frattini F et al (2005) Long-term effects of an aggressive

rhythm control strategy in patients with permanent atrial fibrillation and advan- ced heart failure. Heart Rhythm 2:S116 (abs)

28. Stevenson WG, Stevenson LW (2004) Atrial fibrillation and heart failure – five more

years. N Engl J Med 351:2437–2440