Serum metabolic profiling in rheumatic heart disease and degenerative aortic stenosis

Metabolomics enables the characterisation of pathogenic and diagnostic biomarkers in cardiovascular disease (CVD). Given the high prevalence of rheumatic heart disease (RHD) and degenerative aortic stenosis (AS) in Africa, we investigated potential discriminant metabolic biomarkers in individuals with severe RHD and AS undergoing valve replacement and compared them to those in matched controls. Untargeted metabolomics of serum samples showed that seven metabolites that were differentially expressed in RHD patients were independent of the patients' baseline characteristics (covariates) and could differentiate RHD patients from healthy controls (AUC > 0.7). Four metabolites could differentiate AS patients from controls (AUC ≥ 0.7). Of the perturbed metabolites in RHD and AS, 7-HOCA and deoxycholate showed a moderate association with left ventricular ejection fraction. Furthermore, acylcarnitine and ketone body levels were correlated with the left ventricular mass index in RHD and left atrial area in AS patients. Elevated levels of cortisol were associated with the presence of valve calcification in RHD and AS patients. This is a pilot study on rarely studied CVD in sub-Saharan Africa. This study suggested that the metabolites altered in RHD and degenerative AS are not only associated with cardiac remodelling but also involved in major energetic pathways, amino acid metabolism, and inflammation regulation processes.