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

TL;DR

This study aims to better understand rheumatic heart disease and aortic stenosis by using advanced imaging and molecular techniques to identify new biomarkers and disease mechanisms.

Contribution

The study introduces a novel approach combining multiparametric imaging and multiomics to explore biomarkers and pathophysiology in rheumatic heart disease and aortic stenosis.

Findings

The study will use CMR imaging and multiomics to identify novel biomarkers for RHD and AS.

It will explore the suitability of cadaveric tissues as controls in cardiovascular disease research.

The research aims to improve understanding of disease mechanisms and prognosis through comprehensive biomarker profiling.

Abstract

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.

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.

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