The major finding of our study is that out of the many echocardiographic variables that describe LA function, LASr is the most useful parameter in predicting the outcome of CA for paroxysmal AF in patients with normal echocardiographic images.
Multiple factors have been shown to be predictors of AF recurrence after CA. Previous reports demonstrated that LA enlargement is a strong predictor of AF recurrence after CA [18]. LA enlargement provides robust information on the severity of AF, although using this parameter has limitations. The LA volume can increase in patients with diastolic dysfunction, patients with bradycardia, and trained athletes and can decrease as a result of therapy with diuretics. In the present study, there was a significant difference in LAV between the CA failure and complete success subgroups, although the multivariate analysis did not identify LAV as an independent predictor of AF recurrence after CA. Our study group consisted mainly of patients with normal LA dimensions, fifty three (63%) of them had not enlarged (≤34 mL/m²) LA, which suggests that these patients had early stage AF. Nevertheless complete CA success was observed in only part of the group, what indicates that thorough LA function assessment is crucial in selecting patients for CA. Out of various LA function parameters these reflecting LA compliance which is altered by LA fibrosis were the most accurate for predicting CA outcome.
It has been shown that increased LA fibrosis which can be present in not enlarged left atria and in patients with lonely AF, was significantly associated with AF recurrence post CA [4]. Echocardiography with the use of advance imaging techniques allows for the evaluation of the properties and function of the LA wall and therefore may be used in the diagnosis of LA fibrosis. A reduced LAS during the reservoir phase has been shown to correlate with histopathological alterations of the LA wall and the degree of fibrosis estimated by late gadolinium enhancement magnetic resonance imaging (LGE-MRI) [4]. We also previously showed that LASr and LAstf correlated well with the extent of LA fibrosis assessed invasively using electroanatomical mapping and found stronger associations between low atrial potential areas and the parameters characterizing LA diastolic function (LASr, LAstf) than between the same areas and the parameters characterizing LA systolic function (LASct, LAAv, A, a') [15].
The LA mechanics in predicting the outcome after CA in patients with AF have been analyzed in several studies. Recently, Koca et al reported that LA global longitudinal strain (LA-GLS) and LAV index were independent parameters predicting AF recurrence after cryoablation with the cutoff value of 18.1%, LA-GLS had sensitivity of 92.6% and specificity of 85.7% to predict AF recurrence [19]. The optimal cutoff value in our study for prediction of benefit from CA was 23% (84.6% sensitivity and 92.6% specificity) and for prediction of complete success of CA - 28% (79.1% sensitivity and 83.8% specificity). Moreover, Koca et al did not take into consideration the complexity of the LA function and out of LA deformation parameters only reservoir strain was analyzed.
Consistent with previous results, our study indicates that LASr has a high prognostic value as a predictor of AF recurrence after CA [20]. Ma XX et al analyzed in the meta-analysis clinical relevance of LA strain to predict recurrence of AF after CA in eight studies and documented the usefulness of LA strain in identifying patients with high risk of AF recurrence after CA. Results obtained in the present study are confirmatory, although out of eight analyzed studies, six included patients both with paroxysmal and persistent AF. During AF, LA function during the reservoir and conduit phases is severely impaired, and systolic function does not exist: hence a reduction in LASr is observed during AF. Reduced LAS in AF occurs mainly due to atrial mechanical function impairment (lack of systole, impairment of diastole), rather than as a reflection of atrial wall properties. We previously reported no significant relationships between low atrial potential areas and echocardiographic LA function parameters in patients examined during AF [15]. The present study included only patients with sinus rhythm during the analysis.
Two studies included in the above-mentioned meta-analysis investigated patients with paroxysmal AF, however there are some differences when comparing with our study. Hwang et al demonstrated that lower LA systolic strain was strongly associated with AF recurrence after CA [21] however LA strain cutoff was not reported. Moreover the study group included only 40 patients and follow-up lasted 9 months therefore some episodes of AF might have been missed. Morris et al showed that both LA myocardial diastolic dysfunction expressed by global LA strain during LV systole (LAGLS) and systolic dysfunction expressed by LA strain rate during LV late diastole could be useful in distinguish patients with high or low risk of recurrence of AF after CA and found LAGLS 18,8% to be cut-off value [22]
Although LAS has been widely used in clinical studies, there were inconsistencies and pitfalls with these assessments. Recently, the standardization of LA deformation using STE has been developed [11] and can shed new light on the results of previous studies. The present study was performed in accordance with the consensus document established by the EACVI/ASE/Industry Task Force. There have been reports that segmental basal LAS [23] or lateral LAS [24] could be useful predictors for AF recurrence after CA, whereas the interpretation of LAS as global strain rather than as segmental strain is currently recommended [11]. Moreover, at the present time, we are able to use echocardiographic reference ranges for normal LA function parameters, taking into account age and sex [25]. In the present study, the values of LAScd and LASct were within normal values, whereas the LASr value was lower than normal.
The success rate of CA of AF depends on many factors, including the definition used for a successful procedure. In the literature, this definition is variable [26]. The strictest definition is the lack of recurrence of any AF or AT during long-term ECG recordings and frequent ECG monitoring with no AA therapy. This definition is the most ambitious goal of CA, and patients fulfilling this definition have probably reduced or even no risk of thrombo-embolic complications as well as no risk of proarrhythmic effects of AA. The identification of such “super responders” would therefore be of great value. On the other hand, it is unrealistic to expect that all patients with apparently successful CA of AF will be completely free from AF recurrence during follow-up, especially when using the very strict 30 second definition of AF. Moreover, in patients with a CHA2DS2VASc >1, stopping of anticoagulation is currently not recommended, irrespective of the results of CA [3]. Thus, the identification of a broader cohort of patients who benefit from CA of AF is also clinically important. We therefore defined four types of CA results (Fig. 2). First one is strict - no AF recurrence off AA. The second is less strict and includes also patients with no AF recurrences but on AA. We are not able to say what was the reason for continuation of AA since the treatment was left to the discretion of attending physician. However these patients had no AF recurrences after ablation and thus, AA were not introduced because of AF recurrence. We speculate that the most frequent reason for not withholding AA after ablation was patient's or attending physician desire to continue this treatment because of fear of AF recurrence but this is only our speculation. However, since these patients had improvement and no AF recurrences, we classified them as “benefited from ablation”. When we used another, strict definition – “complete success”, these patients were included in the group called “remaining patients”.
Moreover, in every day practice there is a group of patients who do have recurrences of AF following ablation, however, episodes are rare, less symptomatic or shorter. These patients feel better than before the procedure which is, for example, depicted as the reduction in the EHRA class. Therefore, we assumed that it would be justified to identify such a group of patients as partial success (third definition of success used in our study) and include them in the efficacy analysis in two different ways.
Our study shows that modern echocardiography can be effectively used to identify responders to CA of AF, irrespective of the definition of efficacy. This finding suggests that a detailed echocardiographic assessment prior to CA of AF may play a major role in selecting patients for this procedure.
In recent years, there has been a growing interest in atrial cardiomyopathy in patients with AF [27]. Structural fibrotic changes in LA can be present at the very early stage of the disease, and traditional echocardiographic images can be normal. Currently, we are able to use many echocardiographic tools to evaluate LA function. There is a need to determine a simple and reproducible parameter to indicate the best candidate for invasive procedure of CA. We showed that LASr has a high predictive value for patients with sinus rhythm and normal echocardiographic images.
LIMITATIONS
First, the study group was relatively small, and duration of follow-up is relatively short. However, the follow-up period was completed in 98% of patients and the number of patients was sufficient to perform meaningful statistical analysis.
Second, there were some difficulties in obtaining high-quality LA images for speckle tracking analysis to estimate the strain rate in all patients. Due to the difficulties with obtaining accurate estimation of LASRcd on the strain rate curves, we decided to exclude this parameter from the analysis.
Third, although we performed three 4-7 days Holter ECG recordings during a one-year follow-up and patients were frequently seen in the outpatient clinic, we might have missed silent episodes of AF because no long-term continuous ECG recordings, such as implantable loop recorders, were used. Finally, we used two techniques for CA of AF – RFCA and CB, which might have influenced the results. However, the outcomes of CA of AF were similar in both groups and there were only a few minor differences in the baseline echocardiographic parameters between the two groups.