DISCUSSION
The main finding of this meta-analysis is that, between AF patients who maintained post-ablation sinus rhythm and those with arrhythmia recurrence, there is a significant difference in baseline LA-PLSsys measured by 2DSTE in at least two segments. According to our findings, a higher pre-ablation LA-PLSsys could identify patients who will benefit more from a PVI procedure. However, these results should be interpreted with caution because of the existing heterogeneity. The magnitude of the effect size decreases as the LAVi increases. In other words, the LA-PLS as a predictor of AF recurrence in patients with a severely dilated LA may be limited. Moreover we provide evidence that methodological issues could be a potential source of bias. Subgroup analysis based on echocardiographic views used and segments assessed, revealed that the effect size estimation is more homogenous in studies using the same methodology. An exception was noticed for studies using the global approach (apical 4 and 2 chambers- 12 segments). In this subgroup heterogeneity remained substantial (I2: 88.2%). Visually, it can be attributed to two studies- Hongning et al.[27] and Hanaki et al.[15] - which are characterized by including patients with extreme (relative to the pooled baseline LA-PLSsys mean±SD: 20.18%±10.77%) pre-ablation strain values (36.95% and 8,64%, respectively). Thus, concern is also raised about test’s utility in such patients. Nevertheless, no confounding effect of baseline LA-PLSsys was documented in meta-regression analysis.
These results are in line with previous reports[30, 31] which have included studies up to 2017. Our study adds to existing knowledge by allowing a more robust effect size estimation, independent of age, sex, comorbidities and PAF status effects. It also addresses the matter of heterogeneity across the existing literature, leading to some interesting observations, regarding the confounding effect of the baseline LAVi and the methodology used for strain quantification in the included studies.
LA enlargement and remodeling, which typically accompany AF, usually in direct proportion to AF burden, are a critical correlate of AF recurrence[32]. Kalifa et al. demonstrated that higher LA stretch constitutes a substrate for AF development, by increasing activation sources at the junction between pulmonary veins and the LA in a sheep model[33]. On the other hand, long-standing ineffective atrial contraction in the setting of persistent AF worsens LA dilatation and electric remodeling and can perpetuate the arrhythmia[34]. The pathophysiology of AF can be, thus, described as ectopic triggering in a reentry atrial environment[35]. The remodeling of the atrial interstitial matrix, which is characterized by increased fibrosis, is a prerequisite for reentry of ectopic depolarizations and the occurrence of AF. Increased fibrosis has been shown to be an independent predictor of left atrial mechanical dysfunction[36]. Reactive deposition of collagen fibers in the interstitium causes massive fibrosis with consequent alterations in normal conduction[37]. Moreover, fibrosis tends to increase progressively, favoring conversion to a permanent form. Prevention of atrial fibroblastic remodeling is fundamental; identification of an advanced stage of fibrosis can guide a specific and focused therapeutic strategy[38, 39]. Consequently, LA strain could be useful in identifying patients with LA structural and functional remodeling, that is favorable for sustaining AF propagation[9].
According to the CABANA trial and other smaller trials (CASTLE-AF, RAAFT-2), CA is associated with a decreased AF recurrence rate than drug therapy[40-42]. On the other hand, the lack of proof of definitive clinical benefit from PVI in the CABANA trial has highlighted the need to select patients more likely to benefit from this procedure. For this reason, more research is needed in order to understand whether risk factor management and lifestyle changes along with a more focused approach to pre-procedural patient assessment may reduce recurrence rates and maximize the benefits gained from ablation.
Echocardiography is a feasible, widely available, highly reproducible and low-cost examination, which may offer important information regarding parameters potentially associated with post-ablation outcome. This meta-analysis suggests that LA-PLSsys appears to be a useful predictor of AF recurrence after CA. However, it is unclear whether a clinically useful cut-off value (with a high positive and negative predictive value for recurrence) may be computed, which could be employed as a criterion to proceed with CA or not. Currently, according to the results of this meta-analysis, there is a number of potential heterogeneity sources which may limit LA-PLSsys clinical value, including methodological differences, patients with severely dilated LA, etc.