Biomarkers for Predicting the Occurrence and Progression of Atrial Fibrillation: Soluble Suppression of Tumorigenicity 2 Protein and Tissue Inhibitor of Matrix Metalloproteinase-1

Abstract

Background. Soluble suppression of tumorigenicity 2 protein (sST2) and tissue inhibitor of matrix metalloproteinase (TIMP)-1 are involved in multiple pathogenic pathways, including cardiac remodeling, which is the main pathology of atrial fibrillation (AF). This study aims to investigate the previously unexplored relationship between the serum levels of sST2, TIMP-1, and AF. Methods. This was a prospective cross-sectional study conducted at the Capital Medical University Affiliated Beijing Anzhen Hospital between June 2019 and July 2020, with a total of 359 participants. The clinical characteristics and laboratory results of the patients were compared, and multivariable ordinal logistic regression was used to evaluate the relationship between serum sST2, TIMP-1, and AF. Results. The participants included 110 patients with sinus rhythm (SR), 113 with paroxysmal AF (the paroxysmal AF group), and 136 with persistent AF (the persistent AF group). It was found that the sST2 levels gradually increased in these three groups, from 9.1 (6.7–12.4 pg/ml) in the SR group to 14.0 (10.4–20.8 pg/ml) in the paroxysmal AF group and to 19.0 (13.1–27.8) pg/ml) in the persistent AF group ( p < 0.001 ). The multivariable ordinal logistic regression model for sST2 and TIMP-1 demonstrated that sST2 had an area under the receiver operating characteristic (ROC) curve (AUC) of 0.797 (95% confidence interval (CI) 0.749–0.846, p < 0.001 ) and TIMP-1 had an AUC of 0.795 (95% CI 0.750–0.841, p = 0.000 ). The multivariable ordinal logistic regression model for sST2 and TIMP-1 showed good discrimination between SR and AF, with an AUC of 0.846, and the addition of clinical factors, such as brain natriuretic peptide (BNP), left atrial diameter, age, and gender, to the biomarker model improved the detection of SR and AF (AUC 0.901). Conclusions. In this cohort study, sST2 and TIMP-1 were associated with AF progression, independent of clinical characteristics and biomarkers. Soluble ST2 and TIMP-1 combined with age, elevated N-terminal-pro hormone BNP(NT-BNP), and an enlarged left atrium were able to demonstrate the progression of AF reliably.

Predictive value of soluble suppression of tumorigenicity 2 in atrial fibrillation: a systematic review and meta-analysis

“…A total of 12 studies were analyzed with 11,961 participants (including 1,707 AF patients and 10,254 controls). The pooled analysis of 10 studies ( 12 , 21 , 24 , 25 , 27 , 28 , 32 , 34 , 36 , 37 ) as a continuous variable indicated that sST2 was associated with the risk of AF occurrence (HR:1.04, 95% CI: 1.02–1.07, P < 0.01; I 2 = 67.8% Figure 2 ). Sensitivity analyses showed that the outcomes were stable ( Supplementary Figure S2A ).…”

“…Table 1 displayed the baseline characteristics of 24 included studies from 2015 to 2022, comprising 14 prospective studies ( 14 , 17 – 23 , 26 , 29 – 31 , 33 , 37 ), 4 retrospective studies ( 24 , 25 , 27 , 32 ), 4 cross-sectional studies ( 12 , 13 , 34 , 35 ), and 2 case-control studies ( 28 , 36 ). Eleven studies were conducted in Asia (China, Thailand, Singapore), 10 studies in Europe (Germany, Poland, Finland, France, Norway, Spain, Sweden, Turkey), and 3 study in America (The united states).…”

“…The included studies used various sources of sST2 reagents and adopted diverse detection strategies (e.g., 15 studies used ELISA to detect sST2, 2 used aspect plus assay, 1 used plasma samples assay, and 1 used duoset immunoassay assay). Concerning the purpose of these studies, 12 studies ( 12 , 13 , 21 , 24 , 25 , 27 , 28 , 32 , 34 – 37 ) evaluated the predictive value of sST2 in occurrence of AF, while 8 studies ( 14 , 19 , 20 , 22 , 26 , 29 , 31 , 33 ) evaluated AF recurrence, 5 studies ( 17 , 18 , 23 , 30 , 37 ) evaluated MACEs following AF.…”

Correlation between Serum Myosin Light Chain 4 Levels and Recurrence after Radiofrequency Ablation in Patients with Atrial Fibrillation

“…35) The recent guidelines for AF diagnosis and treatment indicate that LAD is a more powerful biomarker than several other clinical variables. 36) Among the recruited 85 patients with AF and 90 healthy subjects, we found a significant increase in LAD in patients with AF. MYL4 encodes an important myosin light chain that is specifically expressed in the atrial mass after birth.…”

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion

“…Moreover, in AF patients without concomitant cardiovascular disease, sST2 concentrations were positively associated with LV myocardial strain and T1 mapping indices [108]. Previous studies have demonstrated significant predictability of AF recurrence after cryoballoon and radiofrequency ablation using sST2 [109][110][111].…”