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.