Statistical analysis
In this study, the univariate analysis of the data identified that CK-MB and TnT after ablation with the TnT elevation were the independent predictors of ERAF following single CBA. Comorbidities such as diabetes mellitus and prediabetes were also significant ERAF predictors. It was noted that the patients treated with statins had a substantially increased risk of ERAF as opposed to those who did not have statins prescribed. Furthermore, the results in the univariate analysis indicated that Troponin T (p = 0.043), and CK-MB (p = 0.010) after ablation as well as TnT elevation (p = 0.044) and INR before ablation (p = 0.012) were associated with ERAF. This low myocardial biomarker release could be associated with lower lesion dimensions, and thus worse efficacy of the procedure. Therefore, the biomarker release could indirectly help to estimate cardiac lesion formation. The longer cryoenergy application time in the ERAF group could be the result of difficult PV anatomy and the poor cryoballoon contact.
Interestingly, several similar studies investigating the relation between myocardial injury biomarkers (CK, CK-MB, Tn) and ERAF have been conducted. For example, Kizilirmak et al. [
11] reported that the elevation in CK, CK-MB, and Troponin I levels following CBA was associated with a lower ERAF rate as indicated in 3-month, 6-month and 9-month follow-up visits. Additionally, the increased levels of TnI were correlated with the median temperature. In the multivariate analysis only TnI elevation was the negative independent predictor of AF recurrence (specificity of 90.7% and a sensitivity of 64.3%; AUC 0.816, 95% CI 0.691–0.906). Another study carried out by Aksu et al. [
12] showed that the lower postablation hsTnT level may predict an increased ERAF rate (
p = 0.012). Lim et al. [
13], similarly, found that the extent of TnT elevation as well as hsCRP predicted ERAF within 3 days after ablation but not following 3 months or 6 months. In the study of Casella et al. [
14], by contrast, no significant association was observed between postprocedural TnI, CK-MB levels and ERAF in a 1-month, 3-month, 6-month and 12-month follow-up.
Our analysis has further revealed that the patients with diabetes or in a prediabetes condition had a significantly increased risk of ERAF. Other studies conducted so far have not been able to conclusively estimate the risk of ERAF in this group of patients given conflicting results. Nevertheless, in Chao’s et al. [
15] research it was shown that patients with abnormal glucose metabolism had a greater AF recurrence rate after catheter ablation than those without it (18.5% vs 8.0%;
p = 0.022). These findings were explained by changes in biatrial substrate properties with an intra-atrial conduction delay and a decreased voltage. It is worth noting that in Cai’s investigation [
16] and D’Ascenzo’s et al. [
17] meta analysis diabetes correlated with ERAF but not independently of other cardiovascular risk factors.
Apart from the correlation with diabetes, our results have also indicated that preablative intake of statins was more common in the group of patients with ERAF (
p = 0.0007). The benefit of statin treatment proved to be significant in the prevention of postoperative AF and after electrical cardioversion. Nevertheless, previous studies on statin therapy designed to prevent AF recurrence after catheter ablation come to contradictory conclusions. In Sulaiman’s double blind placebo randomized trial it was found that an 80 mg dose of atorvastatin did not decrease ERAF risk in the first 3 months after the procedure [
18]. In addition, in Dentali’s et al. [
19] metaanalysis statins did not reduce ERAF risk after catheter ablation (RR 1.04; 95% CI 0.85–1.28,
p = 0.71;
I2 = 34%). It appears that larger randomized control trials are required to elucidate these results and obtain more conclusive data. Another finding relates to the pathophysiology of ERAF which depends on many factors. It has been demonstrated that ERAF within the first 3 months after ablation, called also “the blanking period,” is possibly associated with the inflammatory response, incomplete lesion healing, and autonomic nervous system (ANS) modulation [
2]. Themistoclakis et al. [
20] showed that longer AF duration, history of hypertension, left atrial enlargement, permanent AF were significantly associated with ERAF. Likewise, Bertaglia et al. [
21] in their research pointed out that the structural heart disease and the lack of successful anatomical ablation of all targeted PV predicted early atrial tachyarrhythmias recurrence. Lee et al. [
22], by contrast, showed that the presence of multiple AF foci could predict ERAF (
p = 0.013; ratio = 2.24; 95% CI 1.18–4.25). Other research sources provide scoring systems with AF predicators which can foresee the short term AF recurrence risk (i.e. the APPLE, ALARMc, BASE-AF2) and long term recurrence risk (i.e. MB-LATER, CAAP-AF, PLAAF) following ablation [
23].
However, it is still necessary to define the ERAF predictors which would allow for a better prevention system and a more suitable selection of patients susceptible to late AF recurrence. The statistical analysis and ML algorithms of so many parameters may facilitate such a selection prior the procedure, and thus increase its effectiveness. Identifying the patients with ERAF will help devise a better strategy to monitor the heart rhythm following 3 months since the CBA procedure and tailor further anticoagulant and antiarrhythmic treatment. Some factors related to predicting ERAF can also be directly linked to late and very late AF recurrence, which requires further research.