Distinct Biomarker Signatures of CMR-Defined Myocardial Remodeling in Moderate Aortic Stenosis

  1. Jan Wrobel
  2. Jan Paul Janssen
  3. Alina Beckmann
  4. Jasmin Shamekhi
  5. Mohammed Bahaaeldin
  6. Julian Luetkens
  7. Ibrahim Hawwari
  8. Stephan Nienaber
  9. Bernardo Franklin
  10. Malte Kelm
  11. Georg Nickenig
  12. David Maintz
  13. Stephan Baldus
  14. Baravan al Kassou
  15. Tobias Zeus
  16. Lenhard Pennig
  17. Victor Mauri
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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.

Registration

URL: https://clinicaltrials.gov/study/NCT05851209 . Unique identifier: NCT05851209 .

Clinical Perspective What Is New?

  • In patients with moderate aortic stenosis, myocardial remodeling on cardiac magnetic resonance was heterogeneous, and circulating biomarkers showed distinct associations with individual remodeling domains.

  • The matrix-related biomarkers TIMP-1 and Galectin-3 were associated with native T1, whereas NT-proBNP was associated with several remodeling domains.

What Are the Clinical Implications?

  • No biomarker was associated with echocardiographic stenosis severity, suggesting that circulating biomarkers may add information on the myocardium that valve hemodynamics do not capture.

  • If validated in larger cohorts, matrix-related biomarkers such as TIMP-1 could help select patients with moderate aortic stenosis for advanced myocardial tissue characterization.

Article activity feed

  1. Version published to 10.64898/2026.10.26.26366467 on medRxiv