中度主动脉瓣狭窄进展 MODAS 队列方案

Background: Calcific aortic stenosis (AS) is one of the most common and prognostically relevant valvular heart diseases, with a growing global burden driven by population ageing. Prediction of disease progression from moderate to severe AS, which would be instrumental for earlier diagnosis and treatment, remains challenging. At the same time, moderate AS is increasingly recognized as a heterogeneous condition associated with clinically relevant risk, particularly in patients with cardiac damage, heart failure, or rapid disease progression. Conventional echocardiographic parameters incompletely capture the biological heterogeneity underlying AS progression. The MODAS study was established to investigate biomarkers and mechanisms of AS progression and outcome using longitudinal multimodal phenotyping. Methods: The MODAS Study is a prospective, multicenter, longitudinal observational cohort study enrolling adults with moderate calcific tricuspid AS at three tertiary heart valve centers in Germany. Participants undergo standardized baseline assessment including clinical phenotyping, laboratory testing, electrocardiography, transthoracic echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging. Biospecimens are collected for biomarker, immunologic, proteomic, and genetic analyses, including genome-wide association studies and assessment of clonal haematopoiesis. Participants are followed annually for up to 5 years with repeat clinical assessment, laboratory testing, and echocardiography. The primary endpoint is time to progression to severe AS according to 2025 ESC/EACTS guideline criteria or aortic valve replacement for severe AS, adjudicated by the local multidisciplinary Heart Team. Secondary endpoints include all-cause mortality and additional clinical outcome trajectories. Multimodal data integration will be used to develop and validate prediction models for disease progression and outcome. Discussion: The MODAS Study will provide a harmonized, deeply phenotyped longitudinal dataset to improve risk stratification in moderate AS and to identify imaging, inflammatory, and genetic markers associated with rapid progression and adverse outcomes. The study is designed to support future personalized surveillance strategies, improved selection for earlier intervention, and mechanistic understanding of calcific AS progression. Trial registration: ClinicalTrials.gov NCT05851209. Registered on 9 May 2023.