Rhythm- versus rate-control: catheter ablation trials
Given the overall ineffectiveness of antiarrhythmic agents to achieve the ultimate endpoint of rhythm-control， namely， long-term consistent maintenance of sinus rhythm， over the last years multiple studies have investigatednon-pharmacological therapies for rhythm-control of AF.15Surprisingly， very few of these studies have been designed with the specific purpose of comparing ablative therapy versus rate-control.The first study that has formally compared the two treatment strategies was the Pulmonary Vein Antrum Isolation vs AV Node Ablation With Biventricular Pacing for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure (PABA-CHF).16In this trial， a total of 81 patients with congestive heart failure and symptomatic drug-refractory AF were randomized to either pulmonary vein isolation or atrioventricular-node ablation with backup biventricular pacing therapy， which represents an extreme form of rate-control.16 At 6 months， patients assigned to ablation were more likely to have improved quality of life， exercise tolerance and left ventricular function. The results of the PABA-CHF have been replicated in a recently published randomized trial， the Randomized Trial to Assess Catheter Ablation versus Rate Control in the Management of Persistent Atrial Fibrillation in Heart Failure (ARC-HF).17 In the ARC-HF， 52 patients with congestive heart failure and persistent AF were randomized to either ablation or rate-control. At 12 months， the peak VO2significantly increased in the ablation arm compared with rate-control (+3.07ml/kg/min， P =0.018). Catheter ablation also improved the Minnesota score (P =0.019) and BNP (P =0.045)， and showed a non-significant trend toward improved left ventricular ejection fraction (P =0.055). It bears emphasis that both the PABA-CHF and the ARC-HF adopted extensive ablation protocols aimed at targeting areas outside the pulmonary vein ostia. Although based on a relatively small number of patients， the results of the PABA-CHF and ARC-HF are totally in line with what already shown in smaller prospective series evaluating either catheter ablation or atrio-ventricular node ablation with backup pacing in patients with congestive heart failure and AF.
To date， a total of 9 studies (2 randomized trials， and 7 observational studies) have evaluated the benefit of catheter ablation in patients with AF and left ventricular dysfunction.16， 18-25These studies have included a total of 354 patients with left ventricular dysfunction (range of ejection fraction 35% to 43%) and both paroxysmal and persistent AF. Remarkably， all studies reported a significant improvement of ejection fraction at follow-up， accounting for an overall average 11% improvement (P < 0.001) compared with baseline values， when performing a pooled random effect meta-analysis of mean differences.Notably， none of the studies evaluating rate-control in AF patients with congestive heart failure has reported comparable improvements of left ventricular ejection fraction. For instance， in a recent meta-analysis， the overall improvement in left ventricular ejection fraction after atrioventricular nodal ablation and biventricular pacing was of only 2.6% (95% confidence interval， 1.7% to 3.4%).26
The extent to which the benefits of catheter ablation over rate-control reported in trials focused on AF patients with congestive heart failure might be generalized to patients with normal ejection fraction is still unclear， although it entirely plausible that ablation might translate into a substantial benefit also in these subjects.The ongoing Catheter ABlation versus ANtiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial will certainly provide some answers in this sense.
Conclusions
Restoration and long-term maintenance of sinus rhythm constitutes the major endpoint of AF treatment， given the independent association of AF with the risk of thromboembolism， heart failure and mortality. Pharmacological therapy for the rhythm-control of AF is largely ineffective in achieving stable and consistent sinus rhythm， thus resulting in a substantial equivalence with treatments aimed at controlling the ventricular rate during AF (i.e.， rate-control). On the other side， when sinus rhythm is effectively restored with invasive procedures， such as catheter ablation， the benefit of rhythm-control over rate-control becomes clearly manifest. Thus far， there is convincing evidence that catheter ablation is superior to rate-control in AF patients with congestive heart failure. Further studies will evaluate whether such benefits might extend also to patients with normal left ventricular function.
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