To Örebro University

Background: Atrial fibrillation (AF) is associated with significant morbidity and healthcare burden. While some patients remain asymptomatic, others experience debilitating symptoms. Traditional factors such as heart rate and rhythm irregularity do not fully explain this variability, suggesting that additional mechanisms, including inflammation, contribute to symptom severity.

Purpose: We aimed to investigate inflammation-associated protein profiles in patients with symptomatic AF before and after ablation compared to controls.

Methods: This case-control study included 100 patients aged 18–75 years with symptomatic paroxysmal or persistent AF scheduled for a first catheter ablation (pulmonary vein isolation) and 100 age- and sex-matched controls without AF. Symptom burden was assessed using the AF6 questionnaire (score range 0-60) and the modified European Heart Rhythm Association (EHRA) symptom scale. Peripheral blood samples were collected from AF patients both before and the day after ablation, and once from controls. Proteomic profiling was performed using the Olink Target 96 Inflammation panel. In addition, six AF-related proteins—Cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity (hs) C-reactive protein (CRP), cancer antigen 125 (CA-125), hs troponin, and S100-calcium binding protein B (S100B)—were analysed separately. Principal component analysis and linear regression models (adjusted for baseline value, age, sex, rhythm at admission, baseline creatinine, and baseline NT-proBNP) were used to examine biomarker profiles, with significance defined as p<0.05 after Bonferroni correction.

Results: The median AF6 sum score was 23 (IQR: 14-32), and most patients were classified as EHRA III, indicating severe symptoms before ablation. Fifty-two inflammatory biomarkers, including interleukin-6, fibroblast growth factor-21, and interleukin-10 were significantly increased after compared to before ablation. Principal component analysis showed partial separation between AF patients (both pre- and post-ablation) and controls, indicating distinct inflammatory profiles, with some overlap between pre- and post-ablation (Figure 1). Among the six targeted proteins, all were elevated except S100B. In the case-control comparison, 12 biomarkers were significantly increased in AF patients, and NT-proBNP and Cystatin C were elevated in the separate analysis. Twenty-three patients experienced at least one ECG-verified AF recurrence between the end of the three-month blanking period and the six-month follow-up.

Conclusion: Our findings indicate that symptomatic AF is associated with a distinct inflammatory biomarker signature that is further modified by catheter ablation. These results highlight an acute inflammatory response and potential immune modulation post-ablation, underscoring the potential of inflammatory biomarkers in refining personalised management strategies for patients with symptomatic AF.