Xin Chen,1– 3,* Xing Zhong,1,4,* Dan Luo,1– 3,* Yuhua Lei,1– 3 Rui Huang1– 3 

1Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshii, Hubei Province, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshii, Hubei Province, People’s Republic of China; 4Department of Medicine, Hubei Minzu University, Enshi, Hubei Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yuhua Lei; Rui Huang, Email yuhualei0319@163.com; henry0923@whu.edu.cn

Background: Heart failure (HF) is a chronic disease with a poor prognosis, making it extremely important to assess the prognosis of patients with HF for accurate treatment. Secreted modular calcium-binding protein 2 (SMOC2) is a cysteine-rich acidic secreted protein that plays a pathophysiological role in many diseases, including regulation of vascular growth factor activity. It has previously been found that SMOC2 plays an essential role in cardiac fibrosis in our previous preclinical study, but whether it can be used as a clinical marker in heart failure patients remains unclear. The purpose of this research was to evaluate the correlation between plasma levels of SMOC2 and the prognosis for individuals with HF.
Methods: HF patients diagnosed with ischemic cardiomyopathy were enrolled from January to December 2021. Baseline plasma levels of SMOC2 were measured after demographic and clinical features were collected. Linear and nonlinear multivariate Cox regression models were used to determine the association between plasma SMOC2 and patient outcomes during follow-up. All analysis was performed using SPSS, EmpowerStats, and R software.
Results: The study included 188 patients, and the average follow-up time was 489.5± 88.3 days. The plasma SMOC2 concentrations were positively correlated with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), left ventricular end-diastolic diameter (LVEDd), and length of hospital stay and were negatively correlated with left ventricular ejection fraction (LVEF) at baseline. A total of 53 patients (28.2%) were rehospitalized due to cardiac deterioration, 14 (7.4%) died, and 37 (19.7%) developed malignant arrhythmias. A fully adjusted multivariate COX regression model showed that SMOC2 is associated with readmission (HR = 1.02, 95% CI:1.012– 1.655). A significant increase in rehospitalization risk was observed in group Q2 (HR =1.064, 95% CI: 1.037, 3.662, p=0.005) and group Q3 (HR =1.085, 95% CI:1.086, 3.792, p=0.009) in comparison with group Q1. The p for trend also shows a linear correlation across the three models (P < 0.001). SMOC2 was associated with the severity of HF in patients, but not with all-cause deaths and arrhythmias during follow-up.
Conclusion: Plasma SMOC2 is associated with the severity of HF and readmission rate, and is a good predictor of the risk of readmission in patients.

Keywords: SMOC2, heart failure, ischemic cardiomyopathy, readmission rate, myocardial fibrosis