Distinct Biomarker Signatures of CMR-Defined Myocardial Remodeling in Moderate Aortic Stenosis
- 1Department of Cardiology, Angiology, Pneumology and Intensive Care Medicine, Heart Center, University of Cologne, Cologne, Germany; Center for Cardiovascular Me
Abstract
Background: Moderate aortic stenosis (AS) is associated with adverse outcomes, yet the myocardial response to pressure overload varies substantially between patients and is incompletely reflected by valve hemodynamics. We aimed to determine whether circulating biomarkers of myocardial stress, injury, and fibrosis associate with cardiac magnetic resonance (CMR)-defined myocardial remodeling in moderate AS. Methods: Eighty-nine patients with moderate AS prospectively underwent CMR (cine imaging, T1 mapping, extracellular volume fraction [ECV], late gadolinium enhancement [LGE]) with concurrent measurement of NT-proBNP, high-sensitivity troponin T, sST2, TIMP-1, and Galectin-3. Biomarker associations with the phenotype-defining CMR parameters were tested with adjustment for age, sex, and renal function and correction for multiple testing, and patients were additionally classified into 4 hierarchical remodeling phenotypes. Results: Six of 20 biomarker-CMR associations remained significant after correction for multiple testing. NT-proBNP tracked LV mass index (beta=0.50), ECV (beta=0.35), and LGE burden (beta=0.43, all q<0.05). TIMP-1 and Galectin-3 were selectively associated with native T1 (both beta=0.35, q=0.012), and sST2 was inversely associated with LV mass index (beta=-0.27, q=0.046). TIMP-1 (adjusted OR 2.18 per SD, 95% CI 1.37-3.48, q=0.005) and NT-proBNP (OR 2.10, 1.19-3.69, q=0.026) increased with higher hierarchical remodeling phenotype. No biomarker was associated with echocardiographic mean gradient, peak velocity, or indexed valve area after correction. Conclusions: Circulating biomarkers showed distinct associations with CMR measures of myocardial remodeling in moderate AS. Matrix-related biomarkers were associated with native T1, whereas NT-proBNP was associated across several remodeling domains. These signals were not measurably related to valve hemodynamics.
Related
- Integrated serum and synovial biomarker profiling reveals inflammatory and cartilage remodeling signatures in age-restricted knee osteoarthritis.
- Baseline Hemoglobin and Outcomes in Advanced Chronic Kidney Disease with Moderate-to-Severe Myocardial Ischemia: A Secondary Analysis of the ISCHEMIA-CKD Trial
- TRPV1-cardiac afferent ablation after completed myocardial infarction prevents arrhythmogenic remodeling
- AN INTEGRATED HEART-ON-A-CHIP NAM RESOLVES DISTINCT CLINICAL PHENOTYPES OF MYOCARDIAL ISCHEMIA-REPERFUSION INJURY
- Ingramon-Depot Therapy in db/db Mice: The Impact on Local and Systemic Inflammation and Myocardial Remodeling
BibTeX
@misc{wrobel2026distinct,
title = {{Distinct Biomarker Signatures of CMR-Defined Myocardial Remodeling in Moderate Aortic Stenosis}},
author = {J. Wrobel and J. P. Janssen and A. Beckmann and J. Shamekhi and M. Bahaaeldin and J. Luetkens and I. Hawwari and S. Nienaber and B. Franklin and M. Kelm and G. Nickenig and D. Maintz and S. Baldus and T. Zeus and L. Pennig and V. Mauri},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.26366467},
url = {https://www.medrxiv.org/content/10.64898/2026.10.26.26366467v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Distinct Biomarker Signatures of CMR-Defined Myocardial Remodeling in Moderate Aortic Stenosis
AU - J. Wrobel
AU - J. P. Janssen
AU - A. Beckmann
AU - J. Shamekhi
AU - M. Bahaaeldin
AU - J. Luetkens
AU - I. Hawwari
AU - S. Nienaber
AU - B. Franklin
AU - M. Kelm
AU - G. Nickenig
AU - D. Maintz
AU - S. Baldus
AU - T. Zeus
AU - L. Pennig
AU - V. Mauri
PY - 2026
DA - 2026/10/26
PB - medRxiv
DO - 10.64898/2026.10.26.26366467
UR - https://www.medrxiv.org/content/10.64898/2026.10.26.26366467v1
AB - Background: Moderate aortic stenosis (AS) is associated with adverse outcomes, yet the myocardial response to pressure overload varies substantially between patients and is incompletely reflected by valve hemodynamics. We aimed to determine whether circulating biomarkers of myocardial stress, injury, and fibrosis associate with cardiac magnetic resonance (CMR)-defined myocardial remodeling in moderate AS. Methods: Eighty-nine patients with moderate AS prospectively underwent CMR (cine imaging, T1 mapping, extracellular volume fraction [ECV], late gadolinium enhancement [LGE]) with concurrent measurement of NT-proBNP, high-sensitivity troponin T, sST2, TIMP-1, and Galectin-3. Biomarker associations with the phenotype-defining CMR parameters were tested with adjustment for age, sex, and renal function and correction for multiple testing, and patients were additionally classified into 4 hierarchical remodeling phenotypes. Results: Six of 20 biomarker-CMR associations remained significant after correction for multiple testing. NT-proBNP tracked LV mass index (beta=0.50), ECV (beta=0.35), and LGE burden (beta=0.43, all q<0.05). TIMP-1 and Galectin-3 were selectively associated with native T1 (both beta=0.35, q=0.012), and sST2 was inversely associated with LV mass index (beta=-0.27, q=0.046). TIMP-1 (adjusted OR 2.18 per SD, 95% CI 1.37-3.48, q=0.005) and NT-proBNP (OR 2.10, 1.19-3.69, q=0.026) increased with higher hierarchical remodeling phenotype. No biomarker was associated with echocardiographic mean gradient, peak velocity, or indexed valve area after correction. Conclusions: Circulating biomarkers showed distinct associations with CMR measures of myocardial remodeling in moderate AS. Matrix-related biomarkers were associated with native T1, whereas NT-proBNP was associated across several remodeling domains. These signals were not measurably related to valve hemodynamics.
ER -