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A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques

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Item Type:Article
Title:A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques
Creators Name:Mutithu, D.W. and Aremu, O.O. and Mokaila, D. and Bana, T. and Familusi, M. and Taylor, L. and Martin, L.J. and Heathfield, L.J. and Kirwan, J.A. and Wiesner, L. and Adeola, H.A. and Lumngwena, E.N. and Manganyi, R. and Skatulla, S. and Naidoo, R. and Ntusi, N.A.B.
Abstract:INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case–controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.
Keywords:Aortic Valve Stenosis, Biomarkers, Case-Control Studies, Cross-Sectional Studies, Echocardiography, Magnetic Resonance Imaging, Metabolomics, Multiomics, Proteomics, Rheumatic Heart Disease
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:19
Number:5
Page Range:e0303496
Date:13 May 2024
Official Publication:https://doi.org/10.1371/journal.pone.0303496
PubMed:View item in PubMed

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