Catheter Ablation of Atrial Fibrillation in Patients with Heart Failure: Can we Break the Vicious Circle?

Heart failure (HF) management should aim to provide symptom relief, increased exercise tolerance, and reduction of disease-related morbidities and mortality. As atrial fibrillation (AF) relates to worsening of symptoms and increased risk of mortality,1 it warrants maximum consideration. However, although HF and AF are two strongly correlated emerging epidemics, the approach to patients presenting these cardiovascular diseases together remains challenging and cause for concern. Atrial fibrillation and HF often coexist in patients, as they share several pathophysiological links. Patients with AF, caused by the deleterious haemodynamic effects of atrial contraction loss and irregularity of ventricular systole, are more prone to develop HF compared with patients in sinus rhythm (SR).2 In contrast, patients with HF present with incidence of AF more frequently than patients with normal ventricular function, with increased left ventricular filling pressures and left atrial dilation and fibrosis being the ideal conditions for onset and perpetuation of AF. Notably, this link is relevant both in case of reduced left ventricular ejection fraction (LVEF) than in patients with preserved LVEF HF. Therefore, AF and HF can perpetuate each other in a vicious circle, and this mechanism contributes to worsen prognosis when compared with that of a similar patient affected by only one of the two pathologies at a time. In fact, higher mortality was reported among HF patients with AF compared with those in SR. In particular, patients with preserved LVEF HF suffer an even worse negative prognostic effect of AF compared with those with HF and reduced LVEF.3 Patients with AF and concomitant HF also present with higher mortality and thromboembolic events compared with patients with AF without HF.4 Of note, the risk of death and thromboembolic events related to AF is comparably higher in patients with reduced LVEF HF and those with preserved LVEF HF.5 No direct evidence favour rhythm control by antiarrhythmic drugs compared with rate control: rhythm control by antiarrhythmic drugs achieves poor results and exposes patients to side-effects. The Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial observed no difference in cardiovascular mortality, death from any cause, and worsening of heart failure between patients with LVEF ≤35% and symptoms of HF randomized to rate or rhythm control.6 For this reason, guidelines recommend, as in patients without HF, that management of AF should start with rate control and, only in case of persistent symptoms, rhythm control. In contrast, a substudy of the AFFIRM trial7 suggested that the benefit in terms of survival deriving from SR maintenance (HR 0.53, 99% CI 0.39–0.72) was neutralized by the detrimental effects of antiarrhythmic drugs (HR 1.49, 99% CI 1.11–2.01). In addition, recent observational studies broaden the possibility that rhythm may perform better than rate control, which is associated with longer survival8 and decreased incidence of stroke.9 In the general population, duration of AF eventually leads to cerebral lesions, which can be detected by MR scans, and cognitive performance impairment.10 Given these assumptions, AF catheter ablation, as rhythm control strategy, has been increasingly proposed over the last decade. However, despite the epidemics of HF and AF, few patients presenting both these diseases are managed by AF catheter ablation. Catheter ablation of AF in HF patients should be considered when amiodarone fails to control symptoms. Bearing in mind that assessment of AF-related symptoms may be challenging, with overlapping HF symptoms, and that more extensive left atrium ablation may be needed in addition to isolation of the sole pulmonary veins (PV),11 the need for an individual and informed decision for catheter ablation in HF patients becomes imperative. However, in the case of asymptomatic AF,12 as supported by current guidelines recommending AF ablation for symptoms management, it remains uncertain whether the procedure can provide substantial benefit. Finally, previous statements suggesting a lower likelihood of SR maintenance following AF catheter ablation and higher procedure-related risk in HF patients do not seem to be confirmed in several recently published studies. Given the paucity of data focusing on this subgroup of patients, recommendations derive mostly from the three meta-analyses available that have differently pooled data on AF catheter ablation in HF patients. The first meta-analysis13 included seven observational studies and one randomized trial (n = 1,851). Follow-up ranged from 6 to 27 months. In patients with HF 28–55% were free from AF at follow-up after one AF catheter ablation, increasing to 64–96% after a mean of 1.4 procedures. The relative risk for recurrent AF in those with vs. without HF was 1.5 (95% CI 1.2–1.8, P < 0.001) after one procedure and 1.2 (95% CI 0.9–1.5, P = 0.2) after multiple procedures. No difference in complications was observed in patients with (3.5%) vs. without (2.5%) HF (P = 0.55). The second meta-analysis14 focused, instead, on LVEF changes following the ablation procedure. A total of 354 patients, mean age 49–62 years, with LVEF ranging from 35% to 43% were included. Their LVEF improved after ablation by 11.1% (95% CI 7.1–15.2, P < 0.001). The proportion of patients with coronary artery disease was inversely related to improvement in LVEF (P < 0.0001). Eventually, in the largest meta-analysis available on this topic, the outcome of AF catheter ablation improves, especially when performed early in the progression of both AF (P = 0.030) and HF (P = 0.045), providing long-term benefits on LVEF and reducing the proportion of patients who would subsequently maintain a LVEF <35% (P < 0.001).15 Supporting these data, one long-term multicenter study16 performed on 196 patients with impaired LVEF has reported, following PV isolation and, in 85% of the cases, additional ablation lines in the left atrium, that 62% of the patients were arrhythmia free after about 4 years—a percentage equivalent to that reported in similarly long follow-up studies in patients without HF.17 Overall, the strongest predictors of rhythm control failure are enlarged left atrium and increased duration of arrhythmia. This finding is not surprising, as these parameters reflect an advanced structural disease involving both left atrium and left ventricle, characterized by a greater extent of fibrosis and lower recovery capabilities. To date only one randomized controlled trial has directly compared, specifically in HF patients, the ideal rate control strategy (and not ‘standard care’)—AV node ablation preceded by cardiac resynchronization therapy (CRT)—to control rhythm by AF ablation. The PABA-CHF18 trial enrolled 81 patients with symptomatic refractory AF, LVEF <40% and New York Heart Association (NYHA) class II–III. One arm of the study underwent PV isolation, the second AV node ablation preceded by CRT. After 6 months follow-up, rhythm control patients reported higher LVEF (35% vs. 28%, P < 0.001), 6-min walking test distance (P < 0.001), and Minnesota Living with HF questionnaire increase (P < 0.001) compared with patients undergoing AV node ablation and CRT. These findings support the beneficial role of SR among these patients, deriving not only from regularization of the ventricular systoles (that CRT also provides)19 but also from maintained atrial mechanical function (also, perhaps, reducing the risk of thromboembolic events). While awaiting currently ongoing randomized controlled trials specifically investigating the role of AF catheter ablation in the setting of HF [e.g. Catheter Ablation versus Standard Conventional Treatment in Patients with LV Dysfunction and Atrial Fibrillation (CASTLE-AF); AF Management In Congestive HF with Ablation (AMICA); Ablation vs. Amiodarone for Treatment of Atrial Fibrillation in Patients with Congestive Heart Failure and an Implanted Cardioverter Defibrillator/CRT Device (AATAC-AF in HF)], it can be stated that AF catheter ablation presents the potential to gain a significant role in HF management for the following reasons. First, AF and HF are two emerging epidemics that often coexist. Based on the extremely scarce literature focusing on this topic it is clear that, to date, the treatment of AF and HF do not consider their intrinsic links and this, in any case, is limiting. Second, AF catheter ablation is a safe procedure and can be performed with a low complication rate in patients with complex atrial substrate, comorbidities, and frailty such as patients with HF. Third, AF catheter ablation, by maintaining SR, increases LVEF over both short- and long-term follow-up. This finding is not surprising: interruption of the vicious circle between AF and HF by restoration of regular cardiac cycles and normal atrial mechanical function are likely to slow or even interrupt the negative electrical and structural remodelling of the failing heart. Fourth, AF catheter ablation is related to significant improvement in quality of life, functional class, and exercise tolerance. However, a some points are lacking clinical evidence and are still under debate. First, the impact of AF ablation on the risk of stroke in HF patients is still unknown, and with HF being a clear independent predictor of increased thromboembolic risk, anticoagulation is still pivotal as a stroke prevention strategy.20 Second, ablation protocol, PV isolation alone and/or additional non-PV targets, as in the general population, need to be tested in prospective randomized trials on HF patients. Third, randomized studies are encouraged to precisely define the optimal timing of AF ablation during natural HF course, especially if this may affect the long-term prognosis of these patients, potentially influencing referral for device implantations, such as implantable cardioverter defibrillators and CRTs.