A Study Protocol to Characterise Pathophysiological and Molecular Markers of Rheumatic Heart Disease and Degenerative Aortic Stenosis Using Multiparametric Cardiovascular

Daniel W. Mutithu, Olukayode O. Aremu, Dipolelo Mokaila, Tasnim Bana, Mary Familusi, Laura Taylor, Lorna J. Martin, Laura J. Heathfield, Jennifer A. Kirwan, Lubbe Wiesner, Henry A. Adeola, Evelyn N. Lumngwena, Rodgers Manganyi, Sebastian Skatulla, Richard Naidoo, Ntobeko A. B. Ntusi

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.

Valvular heart disease (VHD) in sub-Saharan Africa (SSA) is mainly secondary to rheumatic heart disease (RHD), degenerative aortic stenosis (AS) and congenital VHD, most commonly involving the bicuspid aortic valve (BAV) [1]. The prevalence of RHD is remarkably high in low- and middle-income countries (LMICs), making it the most common cause of heart failure in young individuals in LMICs [2]. According to the Global Burden of Disease Study, the incidence rates of RHD have remained stable (changes in age-standardised prevalence 0–1% between 1990 and 2019), while the incidence rates of nonrheumatic VHD increased between 1990 and 2019 [3].

Materials and Methods
This study is designed to characterise VHD patients with mild and severe RHD and degenerative AS based on clinical profiling, CMR, histological parameters, and molecular biomarkers (Fig 1). This study will test the hypothesis that RHD and degenerative AS exhibit distinct pathophysiological mechanisms and follow different molecular processes, as detected by CMR, autophagy, proteomics, and metabolomics profiles. Furthermore, this study will test the hypothesis that there are different molecular signatures associated with mild and severe VHD, and these signatures can be used for early detection.

RHD is endemic in LMICs and SSA. The prevalence of degenerative AS is on the rise in SSA due to the increasing prevalence of ASCVD risk factors (diabetes, hypertension, smoking, dyslipidemia, and obesity). The confluence of the two valvular heart diseases in Africa puts strain on the existing healthcare systems. Therefore, our study aims to describe the pathophysiological imaging markers in RHD and AS patients. Furthermore, we intend to investigate the pathogenesis of RHD in contrast to degenerative AS and identify molecular markers for early detection and diagnosis to determine the molecular pathomechanisms involved and to identify potential therapeutic targets.

Citation: Mutithu DW, Aremu OO, Mokaila D, Bana T, Familusi M, Taylor L, et al. (2024) A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques. PLoS ONE 19(5): e0303496. https://doi.org/10.1371/journal.pone.0303496

Editor: Mohanad Alkhodari, University of Oxford, UNITED KINGDOM

Received: January 8, 2024; Accepted: April 26, 2024; Published: May 13, 2024

Copyright: © 2024 Mutithu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.

Funding: This research is funded through a Blue Skies research grant from the National Research Foundation to SS (Grant Numbers 104839 and 105858) https://www.nrf.ac.za/. NABN gratefully acknowledges funding from the National Research Foundation (https://www.nrf.ac.za/), South African Medical Research Council (https://www.samrc.ac.za) and the Lily and Ernst Hausmann Trust. The funders has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.