Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are two growing epidemics that will continue to frequently coexist as our population ages. Both entities share a number of risk factors and a common pathophysiology involving tissue fibrosis and electrical remodeling.¹ They also synergistically alter the prognosis and treatment of affected individuals, increasing the risk of stroke, heart failure hospitalization, and death.² The loss of atrial contraction in AF reduces cardiac output and impairs diastolic filling, resulting in further hemodynamic compromise in patients with heart failure. Moreover, atrial tachyarrhythmias can induce or exacerbate preexisting ventricular dysfunction,³ and HFrEF by itself promotes left atrial structural and electrical remodeling, thereby increasing the risk of AF.

Maintaining sinus rhythm in patients with AF prevents further hemodynamic deterioration and improves quality of life. Unfortunately, pharmacological rhythm control in patients with AF and HFrEF remains controversial especially in the light of the main results of the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial⁴ and the DIAMOND-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide—Congestive Heart Failure) trial,⁵ both of which failed to show reduction in mortality compared with rate-control strategy. Amiodarone and dofetilide were respectively the main antiarrhythmic drugs tested in those trials and remain the only pharmacological options available in patients with HFrEF according to the international guidelines. These drugs face modest efficacy at maintaining sinus rhythm along with high rates of toxic adverse effects and medication intolerance.

Over the last 15 years, a large body of literature has addressed the effect of catheter ablation (CA) as an alternative to antiarrhythmic drugs for the maintenance of sinus rhythm in patients with AF and HFrEF. Multiple small trials suggested improved left ventricular performance after CA.^6-8 Recently, the AATAC-AF in Heart Failure (Ablation vs. Amiodarone for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted ICD/CRTD) multicenter randomized trial⁹ randomized patients with HFrEF (<40%), persistent AF, and a dual chamber cardioverter defibrillator or cardiac resynchronization therapy defibrillator to CA (102 patients) or amiodarone (101 patients). Of the patients in the CA group, 80% received pulmonary vein isolation plus posterior wall isolation. Patients were followed for a minimum of 24 months. At the end of the study, 70% of the patients in the CA group were free from AF after an average of 1.4 +/- 0.6 procedures, in comparison with 34% in the amiodarone group. There was a 45% relative risk (RR) reduction in unplanned hospitalization (RR 0.55; 95% confidence interval [CI], 0.39-0.76). In addition, there was a significant 56% RR reduction for mortality in patients receiving CA (RR 0.44; 95% CI, 0.20-0.96; number needed to treat = 10 patients). This was the first multicenter randomized study showing that in patients with HFrEF and persistent AF, CA was superior to amiodarone at maintaining freedom from AF and reducing unplanned hospital admissions and overall mortality.

More recently, the CASTLE-AF (Catheter Ablation Versus Standard Conventional Treatment in Patients With Left Ventricular Dysfunction and Atrial Fibrillation) trial¹⁰ was the first trial to evaluate the hard primary endpoint of death or hospitalization for heart failure in patients with symptomatic paroxysmal or persistent AF and HFrEF (left ventricular ejection fraction [LVEF] ≤35%) with an implanted defibrillator. Patients had failed, not tolerated, or were unwilling to take antiarrhythmic drugs. They were randomly assigned to CA (179 patients) or medical therapy (184 patients). CA consisted of pulmonary vein isolation with additional lesions delivered in 51.7% of the cases. A rhythm-control strategy was used in about 30% of the medical-therapy group. The mean follow-up duration was 37.6 +/- 20.4 months. The primary endpoint was significantly reduced in the CA group compared with the medical therapy group (28.5% vs. 44.6%; p = 0.006; number needed to treat = 8.3). There was a benefit in all-cause mortality alone, driven by a significantly lower rate of cardiovascular death in the CA group (11.2% vs. 22.3%; hazard ratio 0.49; 95% CI, 0.29-0.84). A subgroup analysis showed a significant interaction between the LVEF and the primary endpoint, implying that patients with an LVEF <25% were less likely to benefit from CA than those with LVEF ≥25%. In the CA group, 63% of patients were in sinus rhythm at 60 months versus 22% in the medical-therapy group. The recent contribution of the AATAC-AF in Heart Failure and the CASTLE-AF trials suggests that maintenance of sinus rhythm has a beneficial effect on hard clinical endpoints when achieved with CA compared with medical rhythm and rate control. A recently published meta-analysis¹¹ including 856 patients from 7 trials reported that CA was associated with approximately 50% reduction for all-cause mortality in patients with AF and HFrEF along with improvement in LVEF, quality of life, and functional capacity. Importantly, the cumulative complication rates appeared comparable between the CA and the conventional treatment groups.

The 2017 HRS/EHRA/ ECAS/APHRS expert consensus statement on catheter and surgical ablation of atrial fibrillation recommends that "it is reasonable to use similar indications for AF ablation in selected patients with HF as for patients without HF" (Class IIa, Level of Evidence B-R).¹ The growing data supporting a mortality benefit for CA in patients with AF and HFrEF will likely be further highlighted in the future society recommendations documents. It is now clear that restoration of sinus rhythm with CA spares patients with HFrEF the harmful effects of antiarrhythmic drugs, improves left ventricular performance and quality of life, and reduces mortality. Additional data particularly incorporating myocardial scar and remodeling imaging, as well as clinical risk stratification tools, might help physicians better select which patients with AF and HFrEF are most likely to benefit from CA.

References

1. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017;14:e275-e444.
2. Mamas MA, Caldwell JC, Chacko S, Garratt CJ, Fath-Ordoubadi F, Neyses L. A meta-analysis of the prognostic significance of atrial fibrillation in chronic heart failure. Eur J Heart Fail 2009;11:676-83.
3. Gopinathannair R, Etheridge SP, Marchlinski FE, Spinale FG, Lakkireddy D, Olshansky B. Arrhythmia-Induced Cardiomyopathies: Mechanisms, Recognition, and Management. J Am Coll Cardiol 2015;66:1714-28.
4. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008;358:2667-77.
5. Torp-Pedersen C, Møller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999;341:857-65.
6. Hsu LF, Jaïs P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:2373-83.
7. Hunter RJ, Berriman TJ, Diab I, et al. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol 2014;7:31-8.
8. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017;70:1949-61.
9. Di Biase L, Mohanty P, Mohanty S, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial. Circulation 2016;133:1637-44.
10. Marrouche NF, Brachmann J, Andresen D, et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med 2018;378:417-27.
11. Briceño DF, Markman TM, Lupercio F, et al. Catheter ablation versus conventional treatment of atrial fibrillation in patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials. J Interv Card Electrophysiol 2018;53:19-29.

Keywords: Amiodarone, Atrial Fibrillation, Anti-Arrhythmia Agents, Cardiac Resynchronization Therapy, Pulmonary Veins, Atrial Remodeling, Stroke Volume, Risk Factors, Cicatrix, Quality of Life, Phenethylamines, Sulfonamides, Heart Failure, Stroke, Ventricular Dysfunction, Left, Tachycardia, Catheter Ablation, Hospitalization, Defibrillators, Arrhythmias, Cardiac

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