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.
Subject(s)
Aortic Valve Stenosis , Biomarkers , Rheumatic Heart Disease , Humans , Rheumatic Heart Disease/diagnostic imaging , Rheumatic Heart Disease/physiopathology , Rheumatic Heart Disease/metabolism , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/metabolism , Aortic Valve Stenosis/physiopathology , Biomarkers/metabolism , Case-Control Studies , Cross-Sectional Studies , Male , Female , Metabolomics/methods , Echocardiography/methods , Proteomics/methods , Magnetic Resonance Imaging/methods , MultiomicsABSTRACT
BACKGROUND: Chest ultrasound is an emerging imaging modality, for several paediatric pulmonary diseases. SOURCES OF DATA: MEDLINE and EMBASE (1946-47 to 10 March 2017) were searched to collect evidence on the diagnostic accuracy of chest ultrasound, compared to other imaging modalities, for the diagnosis of paediatric pulmonary diseases. AREAS OF AGREEMENT: Eighteen pneumonia studies, comprising 2031 children, were included for meta-analysis; the summary estimate sensitivity was 95.0% (95%CI: 90.7-97.3%) and specificity was 96.1% (95%CI: 89.1-98.7%). AREAS OF CONTROVERSY: Other pulmonary diseases also yielded high sensitivity and specificity, but a meta-analysis could not be conducted due to a limited number of studies includable, and their heterogeneity. GROWING POINTS: Chest ultrasound should be considered as a first-line imaging modality for children with suspected pneumonia. AREAS TIMELY FOR DEVELOPING RESEARCH: Further research should focus on the diagnostic accuracy of chest ultrasound for the diagnosis of paediatric pulmonary diseases, other than pneumonia, comparing against a valid gold standard.
