ABC | Volume 112, Nº5, May 2019

Original Article Correia et al LA stiffness and AF recurrence - a meta-analysis Arq Bras Cardiol. 2019; 112(5):501-508 Figure 2 – Forest plot showing left atrial stiffness as a predictor of atrial fibrillation recurrence after radiofrequency catheter ablation. 0.02 0.1 1 10 50 Favours No Recurrence Favours AF Recurrence 2.10657 0.43012373 0.36493991 0.25352073 0.78936604 1.05744301 28.2% 32.2% 39.6% 100.0% 3.55 [1.81, 6.99] 8.22 [3.54, 19.10] 2.20 [1.08, 4.50] 2.88 [1.75, 4.73] Khurram et al. Park et al. Total (95% Cl) Heterogeneity: Tau 2 = 0.24; Chi 2 = 6.02, df = 2 (p = 0.05); I 2 = 67% Test for overall effect: Z = 3.67 (p = 0.0002) Machino-Ohtsuka et al. Study or Subgroup log[Hazard Ratio] Hazard Ratio SE Weight IV, Random, 95% Cl Hazard Ratio IV, Random, 95% Cl Also, Park et al. 12 showed that in a follow-up period of 16.7 ± 11.8 months, a low LA compliance was associated with a two-fold increased risk of AF recurrence. Also, in the multivariate analysis, adjusting for several factors, LA stiffness was the second most important predictor for AF recurrence after RFCA (HR), only behind persistent AF. Kawasaki et al. 10 showed that in patients submitted to the first or second ablation, the recurrence group had a significant higher LA stiffness than the group with a successful ablation. However, in the multivariate analysis, when analysing patients undergoing the first RFCA, LA stiffness index was not a significant predictor of AF recurrence (OR). Meta-analysis This meta-analysis showed that LA stiffness is associatedwith a higher AF recurrence after RFCA (HR=3.55, 95%CI 1.75–4.73, p = 0.0002), as shown in Figure 2. The heterogeneity test showed that there were significant differences between studies (p = 0.05, I² = 67%). The sensitivity analysis, performed to find the origin of the heterogeneity, revealed that, after removing the study by Khurram et al., 13 who used cardiac magnetic resonance to measure LA stiffness, there was no significant heterogeneity across the studies (p = 0.55, I² = 0%). However, the overall outcome remained the same (HR = 2.64, 95% CI 1.75–3.97, p < 0.00001). A funnel plot (Figure 3) was used to verify the existence of publication bias. There was no obvious asymmetry, suggesting that there was no publication bias. Discussion As mentioned before, catheter ablation has been increasingly considered as a first-line therapy, and therefore, the importance of screening factors has also increased. This systematic review shows that in two 11,13 of four included studies, the LA stiffness was the single most important predictor for recurrence of AF post-ablation on a multivariate analysis, among several factors such as LA volume and persistent AF. Moreover, this meta-analysis, including three studies, showed that LA stiffness is a strong predictor of AF recurrence after RFCA (HR = 3.55, 95% CI 1.75–4.73, p = 0.0002). Therefore, the use of LA stiffness in a preoperative routine may be useful for a close follow-up of patients with higher risk of developing the SLAS and AF recurrence. AF and stiffness of the left atrium Previous studies have shown, despite some limitations, that patients with paroxysmal AF have increased LA stiffness. 14,15 Also, structural remodelling caused by AF leads to LA fibrosis, 16 which may also be a mechanism of LA stiffening. Therefore, an increase in LA stiffness could be an important mechanism of AF genesis and propagation or a consequence of AF episodes. Extensive Catheter Ablation Previous studies have shown that completely circumferentially scarred pulmonary vein by RFCA was associated with less AF recurrence. 17,18 Also, the more scarring overlaps fibrosis, decreasing the amount of unablated fibrotic tissue, the better the arrhythmia free survival. 19 Thus, an extensive ablation appears to be the best option to reduce AF recurrence. However, in a previous study, LA scarring was associated with the development of the SLAS, 5 leading to poor clinical outcomes post-RFCA. LA stiffness as a screening factor for catheter ablation In 1988, Pilote et al. 20 described a condition in patients undergoing mitral valve surgery for LA scarring, characterised by loss of LA compliance, pulmonary hypertension, LA dysfunction and new-onset dyspnea, the so-called SLAS. 5 Subsequently, this syndrome was also reported by Gibson et al. 3 in patients undergoing RFCA, with a relatively rare occurrence (1.4%). Patients with a low-compliant left atrium before the ablation may be more susceptible to develop the SLAS, as RFCA is related to an increase in LA stiffness, 21 probably because the formation of multiple scars in the LA wall induced by the procedure. 22 Therefore, patients with low-compliant left atrium could benefit from a measure of LA stiffness derived from a non-invasive assessment prior to AF ablation, as part of the preoperative screening process, or even routine assessment. This could help to prevent AF recurrence and the SLAS, and to promote a close follow-up of these patients. Marino et al., 9 despite the study limitations, observed a linear relationship between left ventricular (LV) longitudinal strain and invasively measured LA stiffness (calculated during the ascending limb of the V-loop as the ΔLA pressure/ΔLA volume ratio). Since there is an association between the 505