Tissue inhibitor of metalloproteinase (TIMP)-1 predicts negative remodeling and recovery of ejection fraction in acute heart failure with reduced ejection fraction

Abstract

Abstract Background Heart failure with recovered ejection fraction (HFrecEF) is a recently identified phenotype of heart failure, which had lower rates of mortality, heart failure hospitalization, ventricular assist device placement, and heart transplantation compared to heart failure with reduced ejection fraction (HFrEF). Several predictors of HFrecEF had been proposed such as female gender, lower HF duration, nonischemic cause, no left bundle branch block (LBBB), lower EF, and lower N-terminal pro-brain natriuretic peptide (NT-proBNP) in the previous studies. Tissue inhibitors of metalloproteinase-1 (TIMP-1) was a biomarker that regulated the activity of metalloproteinases (MMPs). TIMP-1 was up-regulated during HF and was associated with ventricular remodeling and poor prognosis. However, the predictive value of TIMP-1 and MMP-9 in recovery of EF was yet to be investigated. Purpose The present study aimed at investigating the predictive value of TIMP-1 and MMP-9 of recovery of EF. Methods Subjects with acute decompensated heart failure and reduced left ventricular ejection fraction were eligible for this study. HFrEF was defined as EF <40% and HFrecEF was defined as follow-up EF ≥40% and ≥10% improvement from baseline EF. The biomarkers including NT-proBNP, plasma MMP-9 and serum TIMP-1 were measured in all enrolled subjects at admission. The receiver operating characteristic (ROC) curves and Youden index were used to select the model variables and cutoff values. Binary logistic regression analysis assessed the association between the biomarkers and recovery ejection fraction. Results Among a total of 91 AHF with reduced ejection fraction subjects (70.1±16.2 years, baseline EF 28.9±7.6%), 19 (20.8%) HFrecEF and 72 (79.2%) persistent HFrEF were found at 6 months. TIMP-1 and NT-proBNP were significantly higher in persistent HFrEF compared to HFrecEF. MMP-9 was similar between these two phenotypes of HF. The area under the ROC curve for recovery of ejection fraction of TIMP-1, MMP-9 and NT-proBNP were 0.69, 0.52, and 0.65, respectively. The optimal cutoff value of TIMP-1 according to Youden index was 200.68 ng/ml. In binary logistic regression analysis, TIMP-1 was negatively correlated with recovered ejection fraction as continuous variables [per 1-SD=8.96 ng/ml, odds ratio and 95% confidence interval: 0.99 (0.98–1.00)] and categorical variables [cutoff value 200.68 ng/ml, odds ratio and 95% confidence interval: 0.16 (0.05–0.54)] after adjusting age, gender, EF, acute myocardial infarction, LBBB and NT-proBNP. Conclusions In AHF subjects with HFrEF, TIMP-1 was negatively correlated to the recovery of EF and could be a potential biomarker for the prediction of the recovery of EF. Funding Acknowledgement Type of funding sources: None.