Study protocol for a prospective multicenter longitudinal cohort study on progression of moderate aortic valve stenosis, the MODAS Study
- 1Department of Cardiology, Pneumology and Vascular Medicine, Medical Faculty of Heinrich Heine University, University Hospital Duesseldorf, Duesseldorf, Germany
Abstract
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.
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BibTeX
@misc{phinicarides2026study,
title = {{Study protocol for a prospective multicenter longitudinal cohort study on progression of moderate aortic valve stenosis, the MODAS Study}},
author = {R. Phinicarides and K. Klein and C. Jung and B. S. Franklin and I. Hawwari and V. Mauri and J. Wrobel and S. Baldus and J. A. Luetkens and J. Shamekhi and G. Nickenig and V. Veulemans and M. Kelm and T. Zeus},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.26366513},
url = {https://www.medrxiv.org/content/10.64898/2026.10.26.26366513v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Study protocol for a prospective multicenter longitudinal cohort study on progression of moderate aortic valve stenosis, the MODAS Study
AU - R. Phinicarides
AU - K. Klein
AU - C. Jung
AU - B. S. Franklin
AU - I. Hawwari
AU - V. Mauri
AU - J. Wrobel
AU - S. Baldus
AU - J. A. Luetkens
AU - J. Shamekhi
AU - G. Nickenig
AU - V. Veulemans
AU - M. Kelm
AU - T. Zeus
PY - 2026
DA - 2026/10/26
PB - medRxiv
DO - 10.64898/2026.10.26.26366513
UR - https://www.medrxiv.org/content/10.64898/2026.10.26.26366513v1
AB - 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.
ER -