In the present study, a single ablation of AF was associated with a favourable outcome. Following up 27.2 ± 19.5 months, the overall recurrence rate was 34.0%, with 40.0% for persistent AF patients and 30.1% for paroxysmal AF patients. Multivariate logistic regression analysis indicated that pre-procedural LAVI and eGFR were independent predictors of long-term recurrence. A higher LAVI and a lower eGFR contributed to long-term recurrence after a single procedure for AF in mild to moderate renal insufficiency.
CHADS2, CHA2DS2-VASc, and R2CHADS2 score and AF
Many factors have been proposed as predictors of prognosis after AF ablation, such as congestive heart failure, hypertension, diabetes, previous stroke and sex [
14‐
17]. CHADS
2 and CHA
2DS
2-VASc scores, widely used to predict stroke risks among patients with AF, involve the abovementioned predictors. The R
2CHADS
2 score is a new stroke score that combines the CHADS
2 score and an index of renal insufficiency. Chen et al. [
18] demonstrated a positive relationship between new-onset AF incidence and CHADS
2 scores in a prospective cohort study among Taiwanese patients. Further studies identified a predictive value of CHADS
2, CHA
2DS
2-VASc and R
2CHADS
2 scores for post-ablation recurrence of AF [
18‐
20]. Letsas KP et al. [
21] reported that the predictive accuracy of both CHADS
2 and CHA
2DS
2-VASc was mediocre. Inconsistent with Kornej’s and Chen’s studies, the present study showed no significant differences in CHADS
2, CHA
2DS
2-VASc, or R
2CHADS
2 scores between the recurrence and non-recurrence groups. This finding may be partly ascribed to a rigorous inclusion. Patients with severe comorbidities were excluded. In particular, most of the patients included in this retrospective analysis were mild to moderate renal insufficiency, which had no significant effect on R
2CHADS
2 score.
Renal insufficiency and AF
There is a higher prevalence of AF among patients with different stages of chronic renal disease [
6]. CCr is widely used for the evaluation of renal failure in the clinic, while eGFR is preferred because it is more reliable, cheaper and easier to perform as a preoperative renal function test [
22‐
24]. The R
2CHADS
2 score, involving an index of renal insufficiency determined as CCr, may not effectively evaluate the effect of renal function on the prognosis of AF ablation. The REGARDS study further demonstrated that the prevalence of AF gradually increased with a decreasing eGFR [
25]. In the present study, eGFR was calculated as a renal function index instead of CCr, and multivariate logistic regression analysis showed that pre-procedure eGFR was an independent associated factor of long-term recurrence. Furthermore, multivariate Cox proportional hazard regression model indicated eGFR as an independent prognostic factors for predicting recurrence. This confirmed that eGFR was superior to CCr as a prognostic index of AF ablation. Even mild renal insufficiency may have an unavoidable effect on recurrence after AF ablation.
Active sympathetic and renin–angiotensin–aldosterone systems (RAAS) play important roles in renal insufficiency [
26‐
28], which also involves the pathogenesis of AF [
29]. Norepinephrine released from sympathetic nerve endings enhances the Ca
2+ transient, which may activate the Na
+–Ca
2+ exchange current and induce late phase 3 early afterdepolarization, resulting in focal discharge and AF [
30,
31]. AngII and aldosterone were elevated in patients with renal insufficiency, and both could promote oxidative stress and atrial fibrosis, so-called atrial structural remodelling [
32,
33]. Aldosterone also decreases the transient outward K
+ current and I
to density secondary to the rise in Ca
2+ current, which generates abbreviation of action potential, the so-called atrial electrical remodelling, and induces AF [
34]. Another workable mechanism for eGFR influencing on AF recurrence may be inflammation. Patients with renal insufficiency, even in the early stage, have been reported to have high expression of inflammatory factors, such as hypersensitive C-reactive protein, interleukin-6 and fibrinogen [
35,
36]. In the early stage of renal insufficiency, inflammation could induce myocardial remodelling, which might result in recurrence of atrial arrhythmias after catheter ablation. Lin et al. [
37] found that patients with higher hypersensitive C-reactive protein levels had lower mean bipolar peak voltage in the LA, suggesting extensive atrial remodelling, severe substrate and a greater possibility of non-pulmonary vein triggers. Meanwhile, these patients have a relatively higher mean dominant frequency value and widely-distributed AF nests in the LA. In addition, C-reactive protein may increase reactive oxygen species and enhance LA fibrosis, leading to atrial dilation and atrial dysfunction [
38]. Therefore, the pathological mechanisms above may facilitate the recurrence of atrial tachyarrhythmia after AF ablation.
Left atrial remodelling and AF
Water-sodium retention, hyperactive sympathetic tone and RAAS activation induced by renal insufficiency [
26‐
28] increase LA volume overload and cause atrial remodelling. As reported in previously published studies, left atrial enlargement is the hallmark of atrial remodelling, which facilitates the prevalence of atrial arrhythmias, especially AF [
39,
40]. With the enlargement of the atria, progressive changes in cellular ultrastructure and extracellular matrix (composition and volume) develop. These abnormalities induce myocardial and interstitial fibrosis, local conduction heterogeneities and electrical dissociation between muscle bundles, consequently resulting in the initiation and perpetuation of AF [
39,
41]. The persistence of atrial remodelling, potentially explaining arrhythmogenic substrates, is incremental to the post-procedure recurrence of AF [
42,
43].
Hui-Ling Lee et al. [
44] confirmed a larger LAD was demonstrated to increase the probability of AF recurrence after surgery significantly by a three-year longitudinal study. Despite its procurability, its validity has recently been challenged, as the LA is an asymmetrical cavity. Conversely, biplane LAV provides an overall and reproducible estimation of left atrial size when compared with reference standards such as magnetic resonance imaging. Considering the individual differences, LAVI, calculated as LAV indexed to body surface area, is more comparable in accuracy and reproducibility. Marchese et al. [
45] proved that LAVI was a more exact estimate of LA remodelling than LAD. LAVI was strongly associated with the risk of AF recurrence after cardioversion, with a cut-off of 31 ml/m
2. Kataoka et al. [
46] demonstrated LAVI in predicting failure of the surgical maze procedure for AF patients. However, the role of LAVI in the prognosis of AF ablation has not been well-understood.
In the present study, we found that LAD, LAV and LAVI were higher in the recurrence group. Notably, multivariate logistic analysis demonstrated that LAVI, outperforming either LAV or LAD, was an independent associated factor for predicting long-term recurrence status after catheter ablation of AF. Specifically, increased LAVI contributed to long-term recurrence, with an optimal cut-off of 30 ml/m2, indicating that LAVI, characterized as left atrial remodelling, may be an important determinant for the prognosis of AF ablation. Additionally, multivariate Cox proportional hazard regression also indicated that both eGFR and LAVI are independent prognostic factor for AF recurrence after a single procedure.
Recurrence after AF ablation has remained a puzzle for both doctors and patients. Evaluation of the risk factors for recurrence is crucial in boosting the success rate. In this manner, we found that a decreased eGFR and an increased LAVI had significant adverse effects in predicting long-term recurrence status after a single procedure. Therefore, the preprocedural eGFR and LAVI might be taken into consideration for optimal patient enrolment for AF ablation. Furthermore, patients with eGFR ≤ 55 ml/min/1.732 or LAVI ≥ 30 ml/m2 may be more challenging to maintain sinus rhythm after cardioversion, and require more aggressive clinical interventions.
We acknowledged several limitations. Firstly, patients involved in this study were mainly mild to moderate renal insufficiency (CKD G2-CKD G3a) with mean eGFR 61.4 ± 14.8 ml/min/1.73
2, and these patients with severe renal insufficiency were neglected. The current data may not sufficient to fully assess renal function in the prognosis of AF ablation. According to clinical practice, patients with severe renal insufficiency (CKD G4-5) are mostly complicated with multiple diseases, and most of them are willing to accept conservative drug-treatment. Nevertheless, increasing numbers of patients with severe renal insufficiency are likely to choose AF ablation. It is expected that the sample size will be expanded in the future to evaluate the success rate and postoperative recurrence rate of AF ablation in patients with CKD G4-5, so as to provide reference for the selection of AF treatment options in these patients. Secondly, this study is a retrospective study, all patients were treated with standard surgery, but there were still differences in surgical details among different operators, which might affect the prognosis. In addition, the collected data might be not comprehensive enough, and other important influencing factors, even those related to renal function, may also be omitted. Thirdly, there was a lack of laboratory indicators for further study of the mechanism, such as inflammatory markers, LA fibrosis and LA voltage. Fourthly, AF recurrence rates may be underestimated by ignoring asymptomatic paroxysmal AF due to the limited follow-up period. Mobile health technology may improve the comprehensive management of AF [
47]. Further investigation is needed to determine whether improving renal insufficiency can enhance the long-term success of catheter ablation for AF.