Evidence map›Paper›PMID 40180007›Full record

ArticleActa biomaterialia2025

Tricuspid valve leaflet remodeling in sheep with biventricular heart failure: A comparison between leaflets.

Colton J Kostelnik, William D Meador, Chien-Yu Lin, Mrudang Mathur, Marcin Malinowski, Tomasz Jazwiec, Zuzanna Malinowska, Magda L Piekarska, Boguslaw Gaweda, Tomasz A Timek and 1 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta biomaterialia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. The Tricuspid Valve Maladapts in a Pulmonary Hypertension Rat Model.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Colton J KostelnikDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
William D MeadorDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Chien-Yu LinDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Mrudang MathurDepartment of Mechanical Engineering, The University of Texas at Austin, Austin, TX, USA.
Marcin MalinowskiDivision of Cardiothoracic Surgery, Corewell Health, Grand Rapids, MI, USA; Department of Cardiac Surgery, Medical University of Silesia, School of Medicine in Katowice, Katowice, Poland.
Tomasz JazwiecDivision of Cardiothoracic Surgery, Corewell Health, Grand Rapids, MI, USA; Department of Cardiac, Vascular, and Endovascular Surgery and Transplantology, Medical University of Silesia in Katowice, Silesian Centre for Heart Disease, Zabrze, Poland.
Zuzanna MalinowskaDepartment of Aerospace Engineering & Engineering Mechanics, The University of Texas at Austin, Austin, TX, USA.
Magda L PiekarskaDivision of Cardiothoracic Surgery, Corewell Health, Grand Rapids, MI, USA; Department of Cardiac Surgery, Medical University of Silesia, School of Medicine in Katowice, Katowice, Poland.
Boguslaw GawedaDivision of Cardiothoracic Surgery, Corewell Health, Grand Rapids, MI, USA; Department of Cardiac Surgery, Clinical District Hospital No 2, Faculty of Medicine University of Rzeszow, Rzeszow, Poland.
Tomasz A TimekDivision of Cardiothoracic Surgery, Corewell Health, Grand Rapids, MI, USA.
Manuel K RauschDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA; Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX, USA; Department of Aerospace Engineering & Engineering Mechanics, The University of Texas at Austin, Austin, TX, USA. Electronic address: manuel.rausch@utexas.edu.

Funding

Using an Electrospun Surrogate Model to Investigate Mechanisms of Tricuspid Valve MaladaptationR01HL165251 · NHLBI · UNIVERSITY OF TEXAS AT AUSTIN · PI MANUEL Karl RAUSCH · 2022 to 2026
$4.3M
Human-Specific Prediction, Training, and Visualization Tools for the Tricuspid Valve from Existing DataR21HL161832 · NHLBI · UNIVERSITY OF TEXAS AT AUSTIN · PI RAUSCH, MANUEL KARL · 2022 to 2023
$222k
Tricuspid valve adaptation to right heart disease: A multiscale, histomechanical study in sheepF31HL145976 · NHLBI · UNIVERSITY OF TEXAS AT AUSTIN · PI MEADOR, WILLIAM D · 2019 to 2021
$90k
NHLBI NIH HHS F31 HL145976NHLBI NIH HHS R01 HL165251NHLBI NIH HHS R21 HL161832
6 · The paper itself

Abstract

Tricuspid valve leaflets are dynamic tissues that can respond to altered biomechanical and hemodynamic loads. Each leaflet has unique structural and mechanical properties, leading to different in vivo strains. We hypothesized that these intrinsic differences drive heterogeneous, disease-induced remodeling between the leaflets. Although we previously reported significant remodeling changes in the anterior leaflet, the responses among the other two leaflets have not been reported. Using a sheep model of biventricular heart failure, we compared the remodeling responses between all tricuspid leaflets. Our results show that the anterior leaflet underwent the most significant remodeling, while the septal and posterior leaflets exhibited similar but less pronounced changes. We found several between-leaflet differences in key structural and mechanical metrics that have been shown to contribute to valvular dysfunction. Diseased animals exhibited significantly larger septal and anterior leaflets, thicker anterior and posterior leaflets, and stiffer anterior leaflets. Additionally, the septal leaflet's anisotropy index significantly decreased. Also, the septal and anterior leaflets showed increased collagen fiber dispersion near the atrial surface. As for remodeling markers, alpha-smooth muscle actin (αSMA), Ki67, matrix-metalloprotease 13 (MMP13), and transforming growth factor beta-1 (TGF-β1) were upregulated in spatially and leaflet-dependent patterns. That is, we observed increased expression of these markers within septal leaflets' near-annulus and belly regions, increased expression in anterior leaflets' belly region, and varied expression in posterior leaflets. These findings underscore the need to consider leaflet-specific remodeling to fully understand tricuspid valve dysfunction and to develop targeted therapies for its treatment and more accurate computational models. STATEMENT OF SIGNIFICANCE: Our study is significant as it advances our understanding of tricuspid valve remodeling by providing a comprehensive analysis of all three leaflets in a sheep model of biventricular heart failure. Unlike prior works that focused primarily on the anterior leaflet or generalized leaflet changes, we integrated morphological, histological, immunohistochemistry, biaxial mechanical testing, and two-photon microscopy to quantify differences between all three tricuspid valve leaflets (anterior, posterior, and septal) across multiple functional scales. This comprehensive approach highlights the unique remodeling response of each leaflet. Our findings offer critical insights for developing targeted therapeutic strategies and improving computational models of disease progression.

Indexed as

Heart FailureHeart VentriclesTricuspid ValveAnimalsSheepBiaxial testingHistologyLeaflet-specific remodelingTachycardia-induced cardiomyopathyTwo-photon microscopy

Identifiers

PMID40180007
PMCPMC12065661

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.