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

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.

Prevalence and Impact of HIV Infections in Patients with Rheumatic Heart Disease: A Systematic Review and Meta-Analysis.

Socioeconomic factors such as poor health and poor nutrition in low- and middle-income countries (LMICs) may favour inflammatory reactions, thus contributing to the recurrence of rheumatic fever (RF) and thereby modifying trends in rheumatic heart disease (RHD). Apart from epidemiological studies, studies of HIV infections in RHD patients are limited. This systematic review synthesises data on the prevalence and impact of HIV infections or AIDS on RHD from PubMed, Scopus, Web of Science databases up to April 2021. The outcomes were managed using PRISMA guidelines. Of a total of 15 studies found, 10 were eligible for meta-analyses. Meta-analysis found that 17% (95 % CI 8-33, I2 = 91%) of adults in cardiovascular disease (CVD) cohorts in Southern Africa are HIV positive. The proportion of RHD diagnosed among people living with HIV was 4% (95% CI 2-8, I2 = 79%) for adults but lower [2% (95% CI 1-4, I2 = 87%)] among perinatally infected children. Despite limited reporting, HIV-infected patients with RHD are prone to other infections that may enhance cardiac complications due to poor immunological control. PROSPERO registration number: CRD42021237046.