# Associations of biomarkers with hypoattenuated leaflet thickening after transcatheter aortic valve replacement

**Authors:** David Hesselbarth, Michelle D’Orazio, Giovanni Ciccarone, Diona Gjermeni, Carina Jülch, Philipp Breitbart, Philipp Ruile, Manuel Hein, Marius Wessinger, Mariya Maslarska, Jonathan Rilinger, Christopher Schlett, Fabian Bamberg, Klaus Kaier, Daniel Duerschmied, Torben Pottgiesser, Constantin von zur Mühlen, Dirk Westermann, Christoph B. Olivier

PMC · DOI: 10.1016/j.rpth.2025.103341 · Research and Practice in Thrombosis and Haemostasis · 2025-12-31

## TL;DR

This study explores how blood clotting and inflammation markers relate to leaflet thickening after heart valve replacement, finding some possible links that need more research.

## Contribution

The study identifies potential biomarkers for hypoattenuated leaflet thickening after TAVR, offering new hypotheses for future investigation.

## Key findings

- Shortened clot formation time was associated with HALT but lost significance after correction for multiple testing.
- Increased platelet count, elevated protein S, and higher C-reactive protein levels showed possible links to HALT.
- Findings suggest a potential role for hypercoagulability and inflammation in HALT, though results require further validation.

## Abstract

Patients after transcatheter aortic valve replacement (TAVR) have a high incidence of hypoattenuating leaflet thickening (HALT). However, data on biomarkers related to HALT remain limited.

To identify hemostatic markers associated with HALT following TAVR.

This prospective single-center cohort study assessed hemostatic profiles of patients undergoing TAVR between November 2020 and June 2022 using thrombelastography, light transmission aggregometry, and conventional laboratory markers. The primary outcome was moderate-to-severe HALT (grade 3/4) or reduced leaflet motion (grade 2/3) detected by computed tomography angiography at 6 months post-TAVR.

Of the 107 patients included, 68 had interpretable computed tomography angiography at 6 months. The primary outcome occurred in 14 (20%) patients. Biomarkers were measured at a median of 4 days (IQR, 3-6) after TAVR. Shortened clot formation time (R-time with heparin neutralization) indicated an association with HALT at 6 months (odds ratio [OR], 1.12 [95% CI, 1.00; 1.25]; P = .05) and demonstrated moderate discriminatory ability, with an optimal cutoff of 4.9 minutes (sensitivity 79%; specificity 74%; area under the curve, 0.74 [95% CI, 0.60; 0.89]; P = .005). Increased platelet count (OR, 1.08 [95% CI, 1.01; 1.15]; P = .03), elevated protein S (OR, 1.21 [95% CI, 1.01; 1.44]; P = .04), and higher C-reactive protein levels (OR, 1.19 [95% CI, 1.00; 1.41]; P = .05) also demonstrated associations with HALT. However, after adjustment for multiple testing using the Benjamini–Hochberg procedure, none of these associations was statistically significant.

This exploratory study identified associations between HALT and biomarkers of hypercoagulability and inflammation, which did not persist after correction for multiple testing. These findings should be regarded as hypothesis-generating and warrant confirmation in future studies.

•HALT is frequent after TAVR.•This prospective study used biomarkers and computed tomography to assess HALT after TAVR.•Selected hemostasis and inflammation markers indicated possible associations with HALT.•Findings need further study to clarify the roles of hemostasis and inflammation in HALT.

HALT is frequent after TAVR.

This prospective study used biomarkers and computed tomography to assess HALT after TAVR.

Selected hemostasis and inflammation markers indicated possible associations with HALT.

Findings need further study to clarify the roles of hemostasis and inflammation in HALT.

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** hypercoagulability (MESH:D019851), inflammation (MESH:D007249)
- **Chemicals:** heparin (MESH:D006493)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC12861211/full.md

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Source: https://tomesphere.com/paper/PMC12861211