Main Findings
In this study, we investigated the relationship between RAD and the mid-term outcome of AF after CA. We mainly found RAD was the independent risk factor predicting recurrence of AF after CA only in patients with par-AF. In these patients, RA enlargement is significantly associated with the recurrence after a mid-term follow-up. However, in patients with per-AF, the predictive value of RAD is relatively limited and there was no significantly higher freedom from AF in patients with increased RAD.
Atrial Remodeling as a Predictor of AF Recurrence
The predictive value of RAD might be due to an association between RA anatomical remodeling and outcome of AF after CA. Increased RAD involving RA remodeling may provide the substrate for AF to be sustained. Contributing to atrial enlargement, atrial structural remodeling, particularly fibrosis related to cell death, fibroblast proliferation, and excess extracellular matrix production, is important in many forms of AF [12].Atrial remodeling causes AF progression to permanent forms, so remodeling development is potentially a predictor of treatment response [13].Since Haïssaguerre et al. [14] found the PVs was an important source of ectopic beats initiating frequent paroxysms of AF, many studies focusing on LA has found LA remodeling can predict the recurrence [15, 16].Increased RAD is likely a reflection of RA tissue fibrosis and structural remodeling and atrial remodeling has been found in RA [17, 18].In addition, there is muscular bridge providing interatrial connection between the muscular sleeves of the right PVs and the RA [19]. Thus, it’s reasonable to identify RA remodeling as a predictor of AF, though few studies evaluating the determinants of AF recurrence focused on RA. In patients with per-AF underwent electrical cardioversion, RA size including RA diameter, RA areas, right atrial volume index (RAVI) has been confirmed to predict the recurrence [20, 21], but in patients underwent CA, little is known about the importance of the degree of dilation of the RA on prediction of AF recurrence.
RA Remodeling as a Predictor of AF Recurrence
Moon’s study [9] for the first time to investigated the RA anatomic remodeling assessed with multidetector computed tomography in AF patients found that RA anatomical remodeling, measure as RAVI, might affect the early recurrence after ablation. Houltz et al. [10] reported that RA areas may be important variables in prediction of long-term rhythm outcome after intraoperative ablation for AF. But their study may be limited in that they did not fully distinguish between par-AF and per-AF. As a common sense, AF, as a progressive disease of which the natural history involves evolution from paroxysmal to persistent to permanent forms, has generally more complicated triggering or maintaining mechanisms for the type of per-AF, implicating a more diffuse abnormality of the atrial substrate, which more likely contributed to the recurrence after ablation [12]. Unlike these study including both par-AF and per-AF, our research found RA structural remodeling, measured as RAD which is more clinically available parameter, might affect the outcome only in patients with par-AF at a mid-term follow-up. In patients with per-AF, RAD failed to predict the maintenance of sinus rhythm, though the increased RAD showed the trend of lower success rate. We hypothesized that the phenomenon simultaneously indicated RA remodeling played a more important role only in the pathophysiology of AF at early stage.
Actually, both Akutsu et al. [22] and Wen et al [8] also found that RA remodeling is associated with post-CA recurrence in par-AF. Akutsu et al. found a large RA volume was associated with the recurrence at short-term follow-up of within 6 months. Wen et al found increased RAD was an independent predictor for recurrence only in par-AF patients with LA dilation, indicating that RAD < 35.5 mm is associated with a better recurrence-free survival at over 2-year follow-up. Differently, our study suggested RAD can predict recurrence in patients with par-AF regardless of the LA size, maybe an earlier pathophysical stage of AF than Wen’s study population, at mid-term follow-up, which might complement the Wen’s finding. Similarly, our study found the risk of recurrence increased significantly for RAD above 35.5 mm with 81.3% sensitivity and 54.2% specificity after a mid-term follow-up. Interestingly, this is quite the same clinic cutoff value reported by Wen’s studies with 85.4% sensitivity and 29.2% specificity. Imperfectly, both Akutsu and Wen’s study failed to evaluate the reversible atrial remodeling for the patients without AF recurrence after CA. We found only RAD significantly decreased in patients with par-AF, whereas both LAD and RAD decreased in per-AF. Our research showed that the RAD could decrease significantly after restoring sinus rhythm by ablation after three months, which simultaneously confirmed the important role of RA remodeling in par-AF, as the early stage of AF. Further, as several studies demonstrated [9, 10, 21], although the univariate regression adjusted for several clinical and demographic risk factors, LA size was not identified as a significant predictor of AF recurrence, which is not in accordance with the results from the previous study. This might result from some unmeasured confounders and different study population, ablation strategy or follow-up time.
Clinical implications
Our findings provided additional insights to the understanding of predictor of AF recurrence. In addition to LA remodeling, RA remodeling was also associated with the AF recurrence. The RA size ought to be taken into account in rhythm outcome prediction of ablation treatment. RA remodeling might be a more important factor than left atrial remodeling in the pathophysiology of AF at early stage. Preventing atrial remodeling (so-called upstream therapy) [12] at this stage, intervened in advance for patients with high risk, might suppress the recurrence of the AF, especially in patients of RAD ≥ 35.5 mm. Since the majority of studies mainly focused on LA, the importance of the RA on the outcome of AF after CA might have been seriously ignored. The measurement of preprocedural RA size, combined with the LA size, might provide more reliable prognostic information for patients of AF ready for undergoing ablation. In addition, RA substrate mapping or RA triggers examination during ablation procedure might be beneficial to the outcome in patients with large RA.
Study Limitations
This study was a retrospective and observational study at single center with relatively limited amount of patients and potential selection bias. Thus, what kind of population will show the predictive value of RAD remains unclear. Larger prospective studies are needed to establish predictive utility of RAD in recurrence of AF after CA. In addition, the limited intensity of arrhythmia monitoring on follow-up could have overestimated the chronic success rate. Further, our study used two-dimensional echocardiography to evaluate RA size, which is clinically the most common used method. However, cardiac magnetic resonance is currently considered as the “gold-standard” technique for investigation of the RA and the best approach for accurate RA evaluation is using at least two different imaging techniques [23].