This study investigated the association between a novel inflammatory marker, PIV index, and AF recurrence following CBA. These findings suggest that not only does the PIV index serve as a valuable predictor of early AF recurrence after CBA, but it also surpasses other inflammatory markers in terms of its predictive ability. Additionally, the PIV index showed significant potential for predicting recurrence among patients with various subtypes of AF. Considering their wide availability in laboratory and clinical settings, inflammatory markers, such as the PIV index, offer promise as cost-effective and efficient predictors. Therefore, it is reasonable to recommend these indicators as predictive tools for assessing AF recurrence after CBA, allowing clinicians and patients to perform more comprehensive and accurate risk assessments, while offering improved treatment options.

Inflammation is closely associated with the onset and persistence of AF [16, 17]. The inflammatory response can result in alterations in atrial tissue, such as fibrosis, leukocyte infiltration, and oxidative damage. These changes contribute to electrical and structural remodeling [18, 19], thereby increasing the risk of developing AF. Inflammation plays a pivotal role in both initiation and perpetuation of AF. Through inducing the release of inflammatory cells and factors, inflammation can exacerbate and expedite the electrical and structural remodeling of the atrium, thereby promoting fibrosis associated with AF. This reciprocal relationship between inflammation and AF establishes a detrimental cycle, wherein they mutually reinforce each other. Upon sensing tissue damage, neutrophils promptly secrete inflammatory mediators (such as interleukin (IL)-1, IL-8, TNF-α), which infiltrate into the site of myocardial injury. Simultaneously, it stimulates the production of hematopoietic factors and facilitates neutrophil differentiation in the bone marrow, resulting in an elevated neutrophil count. However, chronic inflammation leads to a reduction in lymphocyte count due to stress-induced responses in vivo, increased apoptosis rates, downregulation of proliferation and differentiation processes, and redistribution during lymphogenesis. Moreover, platelets can also contribute to the initiation and maintenance of AF through their reliance on transforming growth factor-β1 [20].

Inflammation also plays a crucial role in the regulation of calcium stabilization and connexins, both of which have been implicated in the initiation of AF and heterogeneous atrial conduction. Inflammatory pathways mediate cardiomyocyte apoptosis, which is closely associated with the occurrence and maintenance of AF. In summary, inflammation, through various mechanisms, significantly affects atrial electrophysiological and structural changes that may influence immune system function and subsequently contribute to the onset and persistence of AF [21]. Thus, a significant correlation exists between systemic inflammatory diseases and AF, where the exacerbation of the inflammatory condition is linked to an elevated risk of AF. The elucidation of these associations offers a novel avenue for investigating the underlying mechanisms governing AF.

Emerging evidence underscores the pivotal role of inflammation in precipitating bleeding episodes among AF patients, hinting that the activation of a systemic inflammatory state could be a strong predictor of subsequent bleeding occurrences. In a recent cohort of AF patients undergoing direct oral anticoagulant (DOAC) therapy, both the HAS-BLED and DOAC scores exhibited only a moderate capacity in forecasting major bleeding events [22]. Notably, a prior investigation introduced the novel ORBIT-i score, which incorporates the systemic inflammatory status alongside traditional bleeding risk factors, demonstrating superior discriminatory power over the ORBIT and HAS-BLED scores in the same cohort [23]. Herein, the PIV index could emerge as a promising tool for predicting major bleeding complications during DOAC treatment in AF patients.

Studies have shown that inflammatory markers such as hs-CRP, white blood cell count, and IL-6 are closely related to the recurrence of AF after CBA [24]. Increased levels of these inflammatory markers may be related to the postoperative inflammatory response, which in turn affects the recurrence rate of AF. In a study on the relationship between subclinical inflammation and recurrence of AF after CBA [25], it was observed that elevated levels of inflammatory markers such as CRP reduced the success rate of ablation. This suggests that the inflammatory response plays an important role in the occurrence and recurrence of AF. Furthermore, Framingham et al. [26] observed that white blood cell count was related to the incidence and recurrence of AF, confirming the association between inflammation and AF. Inflammatory indices such as SII, NLR, and PLR have also been widely used in recent years to predict the recurrence of AF after different treatment strategies [27,28,29]. These inflammatory indices reflect the inflammatory status of the body and provide a valuable reference for predicting the recurrence of AF.

In a retrospective study [30], NLR predicted the recurrence of AF in patients with a successful sinus conversion rate after catheter ablation. This suggests that NLR, as an inflammatory marker, can reflect the risk of AF recurrence. Moreover, Kus et al. [11] also showed that the SII index was an independent predictor of AF recurrence after direct current cardioversion with a higher predictive value than NLR. This suggests that the SII index may have a higher accuracy in predicting AF recurrence. Clarifying this relationship will offer novel insights and approaches to assess treatment options for patients with AF. Through a deeper understanding of the relationship between inflammation and AF, we can better comprehend the pathogenesis of AF and provide new strategies and programs for its prevention and treatment.

Additional support for the link between inflammation and AF comes from recognizing that inhibiting inflammation achieves anti-arrhythmic effects. The anti-inflammatory effects of glucocorticoids have demonstrated a reduction in both AF recurrence after ablation [31] and new-onset AF after cardiac surgery [32], providing strong evidence for the importance of suppressing inflammation in the prevention and treatment of AF. However, the multitude of complex side effects associated with steroids makes them less than ideal treatment for AF. Colchicine, with its anti-inflammatory effects, has been shown to reduce early recurrence of AF after catheter ablation for a short period [32], providing further evidence that reinforces the association between inflammation and AF. Another promising agent is a sodium-glucose cotransporter 2 inhibitor [33, 34] which directly targets inflammatory pathways such as the nucleotide-binding domain-like receptor protein-3 inflammasome and reduces NLR levels. These findings provide evidence that moderate suppression of the preoperative inflammatory state may improve the outcomes of AF ablation. However, further studies are needed to evaluate the long-term efficacy and safety of these approaches.

Is this index able to accurately reflect the patient’s true condition? Has it taken into account the variability among different populations? Sometimes, the ideal outcomes achieved in clinical studies may differ from the actual results in real-world applications. Although the pan-immune inflammation index has indicated promising value in studies, effectively applying these indicators in real-world clinical scenarios remains a challenge. Further research is needed to validate the role of the pan-immune inflammation index in various diseases and explore how to standardize its measurement and interpretation of results. More large-scale clinical trials are needed to assess its actual effectiveness and suitability in different clinical scenarios.

To our knowledge, this is the first study to explore the use of PIV index in predicting AF recurrence after CBA. The PIV index is an innovative inflammation index [35], which can comprehensively quantify the level of systemic inflammation. It effectively reveals the overall inflammatory response and immune system activation status of patients by calculating four key inflammation-related cell indicators: lymphocytes, neutrophils, platelets, and monocytes. Although the value of this novel biomarker in predicting cardiovascular disease [36] and cancer [37, 38] has been widely recognized, there are still relatively few clinical studies on the use of the PIV index to predict AF recurrence. Additionally, as a novel biomarker, the PIV index holds great potential in clinical practice owing to its low cost, simple calculations, and easy accessibility. Routinely detecting inflammation-related cell markers in patients allows doctors to easily obtain the PIV index data, enabling a more accurate prediction of patient prognosis. This will help improve the quality of care and quality of life for patients.

This was a retrospective study. Because 24-hour Holter monitoring was performed only at the follow-up node, recurrent paroxysmal AF in asymptomatic patients may be neglected. Moreover, the sample size was small. In order to further reveal the relationship between the PIV index and AF recurrence, a large sample, prospective, multicenter study is required.