Abstract
BackgroundHeart 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.MethodsA 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.ResultsSeventeen 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).ConclusionsMass 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.
Highlights
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
Primary dilated cardiomyopathy (DCM) was diagnosed based on the conventional criteria of a left ventricular ejection fraction (LVEF) of less than 45%, a dilated left ventricle and unknown causes of myocardial disease [12]
Patients who had an increase of LVEF ≥5% after 6 months of CRT treatment was defined as responders to CRT [13], patients with an increase of LVEF < 5% were categorized as non-responders
Summary
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. There is no specific biomarker to predict the response to CRT in patients with heart failure. Cardiac resynchronization therapy (CRT) has been shown to be efficacious to improve cardiac function and become a standard treatment for patients with severe heart failure (HF) [1]. A limited number of studies have focused on finding specific biomarkers to predict the response to CRT. Myocardial imaging techniques assessing myocardial mechanical activation time and dyssynchrony are somewhat limited by low sensitivity and large observer variability to predict response to CRT [3]. The evaluation of electrical dyssynchrony using QRS duration (QRSd) was more reliable to predict CRT outcome [4]. Recognition of patients who are likely to benefit from CRT before the device implantation is still challenging
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