Circulating metabolite profiles to predict response to cardiac resynchronization therapy

Abstract

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 nonresponders, 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.

Intestinal microbiota and metabolome perturbations in ischemic and idiopathic dilated cardiomyopathy

“…In addition, there are 14 specific metabolites in IDCM, dominated by amino acids (e.g., isoleucine, leucine, ureidosuccinic acid and pyroglutamic acid), carbohydrates (e.g., erythrose and ribitol) and fatty acids (e.g., 2-methylglutaric acid and azelaic acid). Gong et al [ 53 ] performed a study of serum metabolomic analysis to predict response to cardiac resynchronisation therapy in patients with IDCM. They found that isoleucine and linoleic acid were potential biomarkers in distinguishing responders from non-responders.…”

Metabolic and Metabolomics Insights into Dilated Cardiomyopathy

“…Similarly, a cross-validation analysis also showed a satisfactory and robust performance of the model with AUC of 0.910 in training dataset and 0.880 in the testing dataset, demonstrating potential metabolite markers for predicting HF response to CRT treatment [40]. Another study was conducted by Gong et al [41] using an ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-qTOF-MS) for comprehensive serum metabolomics analyses to help predict response to CRT. In their study, a discovery set of 27 responders versus 24 nonresponders and a validation set of 36 responders and 18 nonresponders were investigated and they reported increased concentrations of isoleucine and linoleic acid and a decreased concentration of tryptophan in response to CRT relative to nonresponders.…”

Plasma Metabolic Profiling Analysis of Heart Failure with Preserved Ejection Fraction Patients Based on UHPLC-MS/MS

“…Tryptophan (Trp) , an essential amino acid, serve as a precursor for various biochemical reactions in the human body, including the synthesis of serotonin, glycools, glucocorticoids and diabetic drugs [26]. Trp metabolism is closely associated with various cardiovascular diseases , with increasing research examining its relationship with Heart Failure(HF) [27][28][29].…”