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.
This study aimed to establish a model that predicts atrial fibrillation (AF) recurrence after catheter ablation using clinical risk factors and biomarkers. We used a prospective cohort study, including 230 consecutive persistent AF patients successfully treated with catheter ablation from January 2019 to December 2020 in our hospital. AF recurrence was followed-up after catheter ablation, and clinical risk factors and biomarkers for AF recurrence were analyzed. AF recurred after radiofrequency ablation in 72 (31%) patients. Multiple multivariate logistic regression analysis demonstrated that tissue inhibitor of metalloproteinase-1 (TIMP-1) and left atrium diameter (LAd) were closely associated with AF recurrence. The prediction model constructed by combining TIMP-1 and LAd effectively predicted AF recurrence. Additionally, the model’s performance discrimination, accuracy, and calibration were confirmed through internal validation using bootstrap resampling (1,000 times). The model showed good fitting (Hosmer–Lemeshow goodness chi-square 3.76138, p = 0.926) and had a superior discrimination ability (the area under the receiver operation characteristic curve0.917; 95% CI 0.882–0.952). The calibration curve showed good agreement between the predicted probability and the actual probability. Moreover, the decision curve analysis (DCA) showed the clinical useful of the nomogram. In conclusion, our predictive model based on serum TIMP-1 and LAd levels could predict AF recurrence after catheter ablation.
BackgroundTissue inhibitor of metalloproteinase-1 (TIMP-1) levels is strongly associated with cardiac extracellular matrix accumulation and atrial fibrosis. Whether serum levels of TIMP-1 are associated with atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) remains unknown.Materials and methodsSerum TIMP-1 levels of patients with AF before they underwent initial RFCA were measured using ELISA. Univariate and multivariate-adjusted Cox models were constructed to determine the relationship between TIMP-1 levels and AF recurrence. Multivariate logistic regression analyses were performed to determine predictors of AF recurrence.ResultsOf the 194 enrolled patients, 61 (31.4%) had AF recurrence within the median 30.0 months (interquartile range: 16.5–33.7 months) of follow-up. These patients had significantly higher baseline TIMP-1 levels than those without AF recurrence (129.8 ± 65.7 vs. 112.0 ± 51.0 ng/ml, P = 0.041). The same was true of high-sensitivity C-reactive protein (3.9 ± 6.0 vs. 1.9 ± 2.8 ng/ml, P = 0.001). When a TIMP-1 cutoff of 124.15 ng/ml was set, patients with TIMP-1 ≥ 124.15 ng/ml had a higher risk of recurrent AF than those with TIMP-1 < 124.15 ng/ml (HR, 1.961, 95% CI, 1.182–2. 253, P = 0.009). Multivariate Cox regression analysis revealed that high TIMP-1 was an independent risk factor for AF recurrence. Univariate Cox regression analysis found that substrate modification surgery does not affect AF recurrence (P = 0.553). Subgroup analysis revealed that female sex, age < 65 years, hypertension (HTN), body mass index (BMI) ≥ 24 kg/m2, CHA2DS2-VASc score < 2, HAS-BLED score < 3, and EHRA score = 3 combined with high TIMP-1 level would perform well at predicting AF recurrence after RFCA.ConclusionElevated preoperative TIMP-1 levels are related to a higher risk of AF recurrence and can independently predict AF recurrence following RFCA.
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