Atrial fibrillation ablation in patients with heart failure

Atrial fibrillation (AF) and heart failure (HF) are among the most frequent diseases in the daily practice of cardiologists, and the management of patients with both conditions is common. An analysis of the Framingham cohort identified that 41% of HF patients had AF episodes during follow-up and 42% of AF patients had an HF¹ episode. The concurrence of these conditions is explained by the fact that both share the same risk factors in their pathophysiology and because the hemodynamic repercussions of AF favor the appearance of HF, and vice versa.

Considering the importance of the topic, Deisenhofer²conducted a review on the evidence and benefits of catheter ablation of AF in patients with HF. As the author mentions, after the first prospective cohort that demonstrated the benefit of ablation in these patients, several randomized clinical trials (RCTs) were published comparing ablation with pharmacological treatment, two of which stand out in relation to the size of the sample space and methodology: AATAC and CASTLE.

The AATAC RCT, published in 2016, compares radiofrequency ablation with pharmacological treatment with amiodarone, including 203 patients with persistent AF and left ventricular ejection fraction (LVEF) less than or equal to 40%. Its result was positive and with important reductions in the risk of the evaluated outcomes, such as absolute risk reduction (ARR) of AF recurrence by 36% (primary result) and ARR mortality of 10% (secondary result), in addition to having Demonstrated improvement in LVEF, reduction in hospitalizations, and improvement in quality of life. The CASTLE study, published in 2018, stood out for its sample size of 393 patients with LVEF less than or equal to 35% and for having demonstrated an ARR of 16% for the “hard” combined primary outcome of death or hospitalization. Subsequently, Sohns et al published the evaluation of two important subgroups of the CASTLE study. The first was the division of the patients into groups according to LVEF, demonstrating that there was a reduction in the primary outcome regardless of the degree of ventricular dysfunction. The second was based on functional class, finding greater benefit in patients with lower functional class, suggesting a greater impact on ablations performed in the initial phase of HF. Another sub-analysis of the CASTLE study by Brachmann et al evaluated the influence of AF load after ablation, demonstrating that patients with AF load < 50% had a reduction in the primary outcome, while those with AF load > 50% they did not benefit from the procedure. In this sub-analysis, the presence of at least one episode of AF lasting more than 30 seconds (the commonly used definition of recurrence after ablation) did not influence the primary outcome, suggesting that the significant reduction in AF load, regardless of paroxysmal recurrence after the procedure, is the main factor responsible for the benefit found.

Regarding the comparison between rhythm control and rate in patients with HF, two articles published after the review article cited here deserve to be highlighted. A sub-analysis of the RCT EAST-AFNET³evaluated 750 patients with symptomatic heart failure undergoing rhythm control or usual care and found an improvement in the composite endpoint of cardiovascular death, stroke, hospitalization for heart failure, or acute coronary syndrome in patients undergoing rhythm control (hazard ratio [HR] 0.74, 95% CI 0.56-0.97). Considering that only 19% of patients in the rhythm control group underwent ablation, this benefit could be even greater. In the subsequent RAFT-AF4 study, the results were similar, although it was interrupted early, with a tendency to reduce mortality and HF events in patients undergoing ablation, but without reaching statistical significance.

Although the CABANA study, the largest RCT comparing ablation and drug treatment, was not designed to specifically evaluate patients with heart failure, it demonstrated benefit with respect to its primary outcome in these patients. Packer et al evaluated the subgroup of patients with heart failure in CABANA, with a total of 778 patients, and found a relative risk reduction of 36% in the primary composite endpoint of death, disabling stroke, major bleeding, or cardiac arrest.

Although the vicious circle between HF and AF is also present in patients with preserved LVEF, the increase in mortality seems to be more pronounced in those with reduced LVEF. In addition, the studies that have evaluated the benefit of ablation in patients with preserved LVEF are observational. Thus, although the body of evidence for these patients is less robust, it also points to an improvement in quality of life and functional class.

Several meta-analyses comparing ablation and drug treatment in patients with AF and HF have already been published, consistent with the beneficial results in terms of mortality and quality of life already mentioned above. However, some subgroup analyzes suggest that not all profiles of patients with HF show the same benefit from ablation. In patients in whom the probability of success in reducing the load of AF is lower, the probability of improving quality of life with this intervention also decreases, such as in patients older than 75 years, with long-standing persistent AF evolution, very large left atrial diameters, extensive area of fibrosis in the left atrium, left ventricular end-diastolic diameter greater than 53mm, and patients as multiple risk factors for AF. In the guidelines on the management of Heart Failure recently published by the European Society of Cardiology, which are mainly based on CASTLE AF and CABANA, catheter ablation is recommended as a class IIa⁵ indication.

In summary, heart failure and atrial fibrillation are two entities that are frequently associated and constitute a vicious circle with a worsening of the quality of life and survival of these patients. Catheter ablation is an effective therapy in patients with heart failure, with a clear benefit over antiarrhythmic drugs that translates into fewer heart failure hospitalizations, decreased mortality, and greater left ventricular reverse remodeling. Although it is an effective treatment, it is important to identify ideal candidates to obtain these results.

References:

1. Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003;107(23):2920-5.

2. Deisenhofer I. Atrial fibrillation in heart failure: Prime time for ablation! Heart Rhythm O2. 2021;2(6Part B):754-61.

3. Rillig A, Magnussen C, Ozga AK, Suling A, Brandes A, Breithardt G, et al. Early Rhythm Control Therapy in Patients With Atrial Fibrillation and Heart Failure. Circulation. 2021;144(11):845-58.

4. Parkash R, Wells GA, Rouleau J, Talajic M, Essebag V, Skanes A, et al. Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. Circulation. 2022;145(23):1693-704.

5. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498.