3.5 Electrophysiological findings in repeat ablation sessions
The LRAF group consisted of 151 patients (23.9%) and repeat ablation sessions were performed in 76 patients in the LRAF group (50.3%). The average duration from the 1st session to the repeat ablation session was 8.6±7.1 months. A reconnection of any of the PVs was identified in 55 of 76 patients (72.4%). No significant difference was observed in the ΔNLR between the patients without a PV reconnection and those with a PV reconnection (1.120±1.323 vs 1.880±3.234, p=0.302, Figure 2A). However, the ΔNLR was significantly higher in the patients with a right PV reconnection than in those without a right PV reconnection (0.914±1.199 vs 2.316±3.615, p=0.032, Figure 2B). No significant difference was observed in the ΔPLR between the patients without a PV reconnection and those with a PV reconnection (8.233±45.00 vs 21.84±74.11, p=0.434, Figure 2C). No significant difference was observed in the ΔPLR between the patients with a right PV reconnection and those without a right PV reconnection (10.20±36.54 vs 24.82±85.21, p=0.349, Figure 2D).
In 55 patients, 1 PV, 2PV, 3PV, and 4PV reconnections in repeat ablation sessions were detected in 12, 23, 7, and 13 patients, respectively. There was a tendency for the ΔNLR to increase as the number of reconnected PVs increased, but there was no significant difference in the ΔNLR between the two groups (Figure 3).
DISCUSSION
The present study highlighted the following results. (1) Higher NLR and PLR changes were associated with a late recurrence of AF/AT after the PVI. (2) An NLR change was significantly higher in the patients with right PV reconnections than in those without right PV reconnections.
Radiofrequency catheter ablation of atrial arrhythmias is known to cause an increase in various markers of inflammation and myocardial injury.19-20 Infiltration of inflammatory cytokines (IL-1, IL-8, TNF-α) into myocardial injury sites induces hematopoietic factors.21-22 These factors stimulate hematopoiesis of neutrophils in bone marrow and a rapid supply of neutrophils from the bone marrow pool. Although segmented cells are the main neutrophils in peripheral blood, in an inflammatory status, the number of stab cells and metamyelocytes increases. Increasing the number of neutrophils also leads to an enhancement in the blood viscosity and hypercoagulability by causing an interaction in the platelets and endothelium.23 Neutrophils suggest nonspecific inflammation and the decrease in the number of lymphocytes reflects the inflammation.24 Low lymphocyte counts have been reported to be related to inflammation.25 The NLR, therefore, more effectively reveals inflammation than the neutrophil count.23 The NLR is a powerful independent indicator of a prognosis in systemic inflammation, atherosclerotic heart disease, and cancer patients.26-27 The PLR is an easy to perform blood test associated with a poor prognosis when elevated in patients suffering from various oncologic disorders.28-29 The PLR is also a strong independent indicator of a prognosis in systemic inflammation such as in critical limb ischemia and collagen disease.30-31
A previous study demonstrated that inflammation was increasingly recognized to play a significant role in the genesis and perpetuation of AF.32-33 Koyama et al. reported an immediate AF recurrence is closely associated with an acute inflammatory process and over 70% of patients with an early AF recurrence have AF episodes 3 months after ablation.11 The relationship between an ERAF and LRAF remains unclear, but several reports have shown the relationship between an ERAF and the durability of the PVI34, and overt ERAFs require the reconnection of a critical number of fibers at the level of the PV-LA junction.35 Probably the reconnection of the left atrium and PVs, presence of non-PV foci triggering AF, and other mechanisms might be associated with LRAFs, but according to the relationship between an ERAF and LRAF, an acute inflammatory response after a PVI is one of the most important risk factors for an LRAF. In our study, the ΔNLR and ΔPLR were higher in patients with an ERAF than in the no-ERAF group, and as a result, the mechanism of the ERAF was possibly associated with an inflammatory process. We also demonstrated that the ΔNLR was higher in patients with a right PV reconnection than in those without a right PV reconnection (0.914±1.199 vs 2.316±3.615, p=0.032, Figure 2B). Recent reports have shown that patients with an ERAF have a significantly higher rate of PV reconnections, in particular of right PV reconnections (82.5% vs 29.2%).35 They also showed that a higher number of right PVI segments with reconnections were observed in those with an ERAF as compared to those without. It is unclear why the right PV reconnections were associated with ERAFs. Presently it remains unclear whether a durable right PV isolation will positively impact the ERAF expression and long-term outcomes. A hypothesis to explain this result is that radiofrequency current is delivered with a high power on the right PV anterior line, which has a thick wall and the posterior line consisting of fiber bundles, while the radiofrequency current is limited on the left posterior line near the esophagus.
In the LRAF group, the ratio of persistent AF (PerAF) patients was significantly higher than that in the no-LRAF group. The plasma BNP level was also significantly higher in the LRAF group than no-LRAF group. Generally the left atrium in PerAF patients causes structural and electrical remodeling and a progressive pressure overload. The level of inflammatory cytokines in heart failure patients was significantly higher than that in patients with a normal heart, but in this study there were no significant differences in the WBCs, hs-CRP, or NLR levels before the ablation between the PAF and PerAF patients. These levels after the ablation and changes from before to after the ablation were similar between the PAF and PerAF patients. These results indicated that the difference between PAF and PerAF did not affect the inflammatory status during the acute phase of the ablation. In the LRAF group, the ratio of a non-PV trigger ablation and an AT ablation was higher than that in the no-LRAF group due to more PerAF patients in the recurrence group, but the total number of energy applications did not differ the between the two groups. A variation was observed in the period from the initial to repeat ablation session (8.6±7.1 months), but this also did not differ between the two groups.
The NLR and PLR can be easily calculated by dividing the neutrophil and platelet counts by the number of lymphocytes, respectively. These measurements are a simple, cost-effective routine test. As suggested by many studies, they may emerge as markers of inflammatory conditions and disease activity. In the present study we demonstrated the relationship between the ERAF/LRAF and ΔNLR/ΔPLR, suggesting an inflammation status. Further studies on inflammation after the PVI and AF recurrence and PV reconnections may be necessary in the future.
CONCLUSION
The NLR and PLR changes were significantly related to early and late recurrences of AF/AT after the PVI. A greater NLR change was significantly associated with a right PV reconnection in the repeat ablation session.