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Abstract：
BACKGROUND: 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.
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.
摘要：
背景：风湿性心脏病（RHD），退行性主动脉狭窄(AS),先天性瓣膜疾病在撒哈拉以南非洲很普遍。在理解疾病机制方面仍然存在许多知识差距，表型分层，和预测。因此,我们旨在通过临床分析来描述患者的特征，成像,组织学,和分子生物标志物来提高我们对病理生理学的理解，诊断,RHD和AS的预后。
方法：在此横截面中，病例对照研究，我们计划招募RHD和AS患者,并将其与匹配的对照进行比较.活着的参与者将接受临床评估，超声心动图,用于循环生物标志物分析的CMR和血液采样。将从接受瓣膜置换的患者获得组织样本，而健康的组织将从尸体中获得。免疫组织学，蛋白质组学，代谢组学，和转录组分析将用于分析循环和组织特异性生物标志物。单变量和多变量统计分析将用于重要生物标志物的假设检验和鉴定。总之,本研究旨在使用多参数CMR成像来描述RHD和退行性AS的病理生理学。除了发现新的生物标志物，并通过组织和血液蛋白质组和代谢组的高通量分析探索与RHD和AS相关的病理机制，并提供使用尸体组织作为心血管疾病研究对照的适用性的概念证明。
方法：在此横截面中，病例对照研究，我们计划招募RHD和AS患者,并将其与匹配的对照进行比较.活着的参与者将接受临床评估，超声心动图,用于循环生物标志物分析的CMR和血液采样。将从接受瓣膜置换的患者获得组织样本，而健康的组织将从尸体中获得。免疫组织学，蛋白质组学，代谢组学，和转录组分析将用于分析循环和组织特异性生物标志物。单变量和多变量统计分析将用于重要生物标志物的假设检验和鉴定。总之,本研究旨在使用多参数CMR成像来描述RHD和退行性AS的病理生理学。除了发现新的生物标志物，并通过组织和血液蛋白质组和代谢组的高通量分析探索与RHD和AS相关的病理机制，并提供使用尸体组织作为心血管疾病研究对照的适用性的概念证明。
