Circulating metabolite profiles to predict response to cardiac resynchronization therapy

BACKGROUND: Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT. METHODS: A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. RESULTS: Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929). CONCLUSIONS: Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.