Discussion
The clinically challenging and thereby pertinent cohort of non-PAF patients would benefit from a validated outcome prediction score used before embarking on a journey of ablative therapy. Analysis of IPOs of non-PAF catheter ablations at a London hospital identified independent predictors of outcome from which the easily calculated FLAME score was derived, relevant to the selection of patients for entry into a catheter ablation programme. When validated among patients undergoing non-PAF catheter ablations in California, it effectively stratified the outcomes of both first and multiple procedures. Patients with high scores had reduced success rates following their first procedure, and their final procedure, with fewer maintaining sinus rhythm despite undergoing more repeat procedures than patients with lower scores. Conversely, among patients with a low score (0–1), a success rate of approximately 80% could be achieved over 5 years of follow-up, and with over 70% of patients requiring just a single procedure.
The FLAME score is the first cohort-specific (non-PAF) outcome prediction score for patients undergoing radiofrequency ablation. MB-LATER and ALARMEc scores have a singular aim focus on predicting outcomes for repeat ablations,8 9 therefore unable to equip physicians to guide a patient at the beginning of their rhythm management journey, which is crucial. The APPLE and CAAP-AF scores have been developed using both derivation and validation cohorts but are not focused on non-PAF, unlike the FLAME score.10 11 Furthermore, the APPLE score allocates a point for impaired LV function (<50% ejection fraction), although current evidence recommending ablation as a treatment strategy for improving systolic function.10 12 Despite the proposal of several scores as predictors of AF recurrence following catheter ablation, the FLAME score is unique—the only externally validated score that can predict both initial and multiprocedural success among non-PAF patients.
The variables we found independently associated with the outcome are intuitively understandable and consistent with existing literature.3–6 13–19 LA diameter is the variable most frequently identified as an independent predictor of non-PAF ablation outcome.3 5 6 13–17 Additional predictors that have been identified previously in the multivariable analysis include female sex,3 4 14–16 duration of AF,3 4 6 13 16 19 and valvular disease.5 Hypertrophic cardiomyopathy has rarely been examined but was a powerful risk factor for failure when tested.16 Structural congenital heart disease is relevant to few, often younger, patients and has not previously been examined, but seems intuitive, and in our experience, an important risk factor for failure. Our finding that left ventricular dysfunction does not predict ablation failure independently is also consistent with most previous studies. With evidence for improvement in functional status with ablation,20 one could argue that for a given FLAME score, ablation is relatively indicated in heart failure patients. In patients with structural congenital heart disease or mitral valve disease, the choices are harder as, while the benefits of sinus rhythm may be greater, the success rate of catheter ablation is lower.
Despite multivariate analysis, important predictive variables may not be identified where data are few or of poor quality, or if the variable is not examined, and the latter situation may lead to alternative confounded variables appearing predictive. Unfortunately, meta-analyses cannot overcome these problems without access to patient-level data. Another critical factor is the inclusion of intraprocedural or postprocedural variables in previous studies, such as AF cycle length, electro-anatomical mapping (ATLAS score),21 termination during ablation or early recurrence of AF (MB-LATER).9 These may impair the ability to detect important preoperative predictive variables due to confounding, for instance, patients with termination during ablation may also have smaller atria. We, therefore avoided this approach.
With the development of consensus around electrically confirmed pulmonary vein isolation with additional substrate modification as the cornerstone of non-PAF ablation, success rates have plateaued in recent years,7 despite ongoing debate around the correct substrate modification techniques to employ.22 Preoperative clinical variables, reflecting the severity of the structural and electrophysiological substrate, seem likely to influence success rates irrespective of the exact ablation technique employed,16 and our findings confirm this concept.
Our results showed that with FLAME score’s 0–4, patients could obtain good long-term results with a mean of <1.5 procedures. However, it is important to remember that such a scoring system can only aid in defining one side of a risk–benefit equation, and it does not necessarily follow that high scoring patients should be denied ablation. Weighed against the likelihood of success must be patient' need, which may be particularly pronounced in those who are most highly symptomatic, intolerant of AADs, or haemodynamically compromised. Additionally, the success rates described in this study reflect the ‘final procedure’ at the time of this study, but not the final clinical outcomes for all patients, many of whom may undergo further procedures in the future. Furthermore, the binary definition of treatment failure used in this analysis may fail to describe the full extent of clinical benefit derived by patients in whom their AF was rendered paroxysmal. However, in the presence of a particularly high FLAME score, the best treatment strategy should be carefully evaluated, and alternative techniques such as surgical or hybrid ablation might be considered.
Limitations
Several questions cannot be answered within the current study design. An exhaustive list of variables was not examined, such as the history and success of cardioversion procedures, and others may exist which reduce success in some patients. Additionally, although previous studies found LA diameter to perform similarly to LA volume,5 23 and it is more commonly calculated, LA volume may improve prediction at extremes of size.23 Like others,5 we found that a binary LA diameter less or greater than 50 mm had predictive power similar to its use as a continuous variable—we chose the latter as, aside from similar statistical power, it seems likely to have a continuous effect. Conversely, duration of non-PAF was tested in a binary manner, in keeping with worldwide definitions and because of the difficulty in determining longer durations accurately; however, we do not know whether it would be more powerful as a continuous variable, nor whether subcategories of persistent AF defined by factors such as a requirement for, or resistance to, electrical cardioversion independently predict outcome. The London population included a minority of patients seen infrequently in other centres, including those with structural congenital heart disease, leading to the unusual finding of the lowest age band having an adverse predictive effect. However, higher age bands had no significant differences in outcome between them, consistent with most other studies,3–6 13–19 and the score effectively stratified the Californian population where none of the patients had structural congenital heart disease. Intraoperative factors were purposely not tested, which may reduce the specificity of the results, and there was heterogeneity of ablation techniques employed and treatment decisions regarding postoperative AADs; however, our intention was to create a score internationally relevant to current and future practice. Additionally, there was a significant difference in follow-up duration between the populations, although interestingly, the separation of Kaplan-Meier curves observed in the Californian population was almost completed within the duration of the London population follow-up. Finally, in line with international recommendations, while we have used the recurrence of ≥30 s of atrial arrhythmia as our outcome measure, other outcomes such as reduction in the burden of AF or change in the quality of life, could be more clinically meaningful and thus the outcomes described may understate the benefit of this procedure to patients.