Metabolic Modulation and Potential Biomarkers of the Prognosis Identification for Severe Aortic Stenosis after TAVR by a Metabolomics Study.

Qiao Li,Mingyue Zhao,Yijian Li,Yong Peng,Jiafu Wei,Yanbiao Liao,Xiaojing Liu,Tianyuan Xiong,Zhengang Zhao,Yuanweixiang Ou,Wei Meng,Chang Liu,Mariantonietta Cicoira,Yuan Feng,Mao Chen,Wen Zheng

doi:10.1155/2020/3946913

Qiao Li, Mingyue Zhao + Show 14 more

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https://doi.org/10.1155/2020/3946913

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Abstract

Objectives To investigate the metabolic profile in patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) and explore the potential biomarkers to predict prognosis after TAVR based on metabolomics. Methods and Results Fifty-nine consecutive AS patients were prospectively recruited. Blood samples from the ascending aorta, coronary sinus, and peripheral vein at before and after TAVR were collected, respectively. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to analyze the metabolic profile before and after TAVR. Influential metabolites were identified by integrating the univariate test, multivariate analysis, and weighted gene coexpression network analysis (WGCNA) algorithm. PLS-DA analysis revealed a significant extremely early (within 30 minutes after TAVR) alterations of metabolites in the ascending aorta, coronary sinus, and peripheral vein. The early (within 7 days after TAVR) changed metabolites in the peripheral vein were involved in purine metabolism, primary bile acid biosynthesis, glycerolipid metabolism, amino sugar and nucleotide sugar metabolism, one carbon pool by folate and alanine, and the aspartate and glutamate metabolism pathway. We used volcano plots to find that the cardiac-specific changed metabolites were enriched to the sphingolipid metabolism pathway after TAVR. Besides, WGCNA algorithm was performed to reveal that arginine and proline metabolites could reflect left ventricle regression to some extent. Conclusion This is the first study to reveal systemic and cardiac metabolites changed significantly in patients with AS after TAVR. Some altered metabolites involved in the arginine and proline metabolism pathway in the peripheral vein could predict left ventricle regression, which merited further study.

Highlights

Aortic stenosis (AS) is a progressive disease which is initially characterized by leaflet calcification and thickening
AS caused a relative myocardial ischemia due to myocardial oxygen supply and demand mismatch from reduced coronary flow reserve because of long-term pressure overload. e hypertrophic cardiomyocyte, increased wall stress, systolic dysfunction, and diastolic dysfunction were seen in patients with AS [1]. ese structural and functional alteration of the heart resulted in derangement of myocardial metabolism including decreased mitochondrial energy production, insulin resistance, and perturbations in amino acid, lipid, and nucleotide metabolism [7]
We found that the metabolic pattern of the ascending aorta and peripheral vein changed significantly immediately and 30 minutes after transcatheter heart valve (THV) implantation compared with preprocedure, which we defined as an extremely early change. e metabolite in the ascending aorta mapped to glycosylphosphatidylinositol (GPI) anchor biosynthesis, vitamin B6 metabolism, glycerolipid metabolism, and sphingolipid metabolism, while the metabolite in the peripheral vein enriched to glycerophospholipid metabolism, glycerolipid metabolism, and purine metabolism

Summary

Introduction

Aortic stenosis (AS) is a progressive disease which is initially characterized by leaflet calcification and thickening. As the progression of AS, maladaptive cardiomyocyte apoptosis and diffused myocardial fibrosis result in heart failure and even multiorgan dysfunction [1]. Cardiac magnetic resonance and echocardiography could reveal the early heart remolding, there were rare serum biomarkers that could reflect heart remolding [2, 3]. Metabolomics, as a well-constructed approach of systemic biology to offer a comprehensive description of lowmolecular weight molecules participating in metabolism, is typically applied in investigating diseases mechanisms and discovering biomarkers [4]. Recent evidence revealed that cardiomyocyte metabolism would change in those patients. Patients with symptomatic severe AS who often exerted remolding and heart failure apparently had changed the metabolic profile [7]. Rare studies investigate the metabolite as a biomarker to reflect myocardial remolding in AS [3]

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Conclusion