Identification of altered metabolites in Rheumatic Heart Disease patients with atrial fibrillation and normal sinus rhythm using untargeted LC-MS metabolomics.

Abstract

Introduction & objective: Rheumatic Heart Disease (RHD) is the commonest cause of atrial fibrillation (AF) in India with higher prevalence in younger population. The clinical significance of the differential metabolites in RHD patients with AF is unknown. This is a tertiary hospital-based study aimed to discover the metabolites associated with AF and normal sinus rhythm (NSR) in RHD patients using untargeted LCMS approach.

Methods: In this case control study, a total of 87 patients (38 persistent AF and 49 NSR) were incorporated after screening, including 12-lead ECG (electrocardiogram), 2D Echo (two-dimensional echocardiography) and a 24-hr Holter examination for NSR patients to exclude silent AF. Blood samples were collected and differentially expressed metabolites were identified using untargeted LCMS approach.

Results: All the patients of our study belong to NYHA (New York Heart Association) classes II and III. The number of female patients was more in both groups. The mean age of the patients was 35.81 ± 7.96 and 29.61 ± 8.18 year in AF and NSR group respectively. 33 metabolites showed significantly altered expression - 15 upregulated and 18 down regulated metabolites. Pathway analysis showed that the altered metabolites were involved in Arginine, Phenylalanine tyrosine and tryptophan biosynthesis, D-Glutamine and D-glutamate, Alanine aspartate and glutamate metabolism, Arginine and proline metabolism.

Conclusions: The findings suggest that differential metabolites in RHD patients may help in identifying the high-risk group and possible therapeutic targets.