Investigation of the relationship between the duration of atrial high rate episodes (AHRE) and inflammatory markers with echocardiographic parameters

Atrial high-rate episodes (AHRE) refer to atrial arrhythmias that meet specific criteria detected by cardiac implantable electronic devices (CIEDs) or wearable rhythm monitoring devices. AHRE has been associated with an increased risk of thromboembolism, heart failure, and cardiovascular mortality. Furthermore, AHRE is considered a precursor to clinical atrial fibrillation (AF). The pathogenesis is thought to involve oxidative stress, inflammatory, and fibrotic changes, leading to atrial remodeling with atrial fibrosis and inflammation. Growth differentiation factor 15 (GDF 15), a member of the transforming growth factor-β (TGF-β) family, plays a critical role in various biological processes such as cell proliferation, differentiation, and apoptozis, and has been independently associated with various cardiovascular phenotypes, including AF. Soluble suppressor of tumorigenicity 2 (sST2), a member of the interleukin-1 (IL-1) receptor family, has been linked to the development of inflammation, oxidative stress, and fibrosis in cardiac tissue. Fibroblast growth factor 23 (FGF 23) activates fibroblast activation by stimulating the TGF-β signaling pathway, leading to fibrosis resulting from abnormal collagen metabolism, such as type I and type III collagen imbalances, which is thought to impact fibrotic changes in the left atrium in AF. The aim of this study is to investigate the relationship between GDF 15, FGF 23, sST2, and echocardiographic (ECHO) findings with the burden of AHRE in patients with detected AHRE. Our study included patients aged 18-80 who presented to Pamukkale University Hospital between May 2024 and December 2024 with a history of dual pacemaker implantation due to complete or high-grade atrioventricular (AV) block and who underwent 24-hour Holter ECG monitoring for suspected arrhythmias. A total of 45 patients with AHRE and 41 individuals without AHRE during follow-up or Holter monitoring were included in the study. AHRE was defined as the presence of an atrial tachyarrhythmia with an atrial rate exceeding 175 bpm lasting at least 5 minutes. Venous blood samples were collected for biochemical analysis of GDF 15, FGF 23, and sST2 from both groups, and comprehensive ECHO examinations were performed. Clinical characteristics, routine blood tests, and medications were obtained from electronic records. The average age of the AHRE group was 68.89±8.32 years (51% female). Age, hypertension, and coronary artery disease were significantly higher in the AHRE group. Left atrial diameter (LA), left atrial volume index (LAVI), interventricular septum thickness (IVS), left ventricular mass index (LVMI), systolic pulmonary artery pressure (sPAB), posterior wall thickness (PW), left ventricular end-systolic diameter (LVESD), E/é ratio, and right atrial area (RA) were significantly higher in the AHRE group. Septal e', lateral e', tricuspid annular plane systolic excursion (TAPSE), TAPSE/sPAB ratio, and glomerular filtration rate (GFR) were significantly lower in the AHRE group. In the AHRE group, GDF 15 and sST2 levels were found to be 9.06±28.79 ng/L and 628.19±1887.58 ng/L, respectively, while in the control group, they were 2.26±4.52 ng/L and 7.44 ± 10.76 ng/L (p=0.0001). Multiple regression analysis identified GDF 15 (p=0.03) and sST2 (p=0.0001) as independent predictors of AHRE. The levels of GDF-15 and sST2 were significantly elevated in the AHRE group and showed a strong positive correlation with the burden of AHRE (r=0.880, p<0.0001; r=0.792, p<0.0001, respectively). Although FGF 23 levels were higher in the control group, it did not show a significant relationship with AHRE. In conclusion, GDF 15 and sST2 emerged as strong biomarkers associated with the presence and burden of AHRE in our study.