# Collagen Fiber Maturity and Architecture in MVP-Associated Fibrosis Quantified by Digital Pathology

**Authors:** Ranan Phookan, Jordan E. Morningstar, Brian Loizzi, Antonia Van Kampen, Cortney Gensemer, Maja-Theresa Dieterlen, Ricardo Spampinato, Louis Petitjean, Mathieu Petitjean, Taylor Petrucci, Roman Fenner, Jake Griner, Kathryn Byerly, Robert A. Levine, Michael A. Borger, Russell A. Norris

PMC · DOI: 10.3390/cells14191536 · Cells · 2025-09-30

## TL;DR

This study uses digital pathology to show that mitral valve prolapse causes significant heart tissue scarring, suggesting earlier surgery could prevent dangerous heart rhythms.

## Contribution

The study introduces digital pathology-based quantitative image analysis to assess collagen maturity in MVP-associated fibrosis.

## Key findings

- Fibrosis in peri-papillary biopsies showed a significantly higher Morphometric Composite Score compared to remote biopsies.
- Collagen fibers in MVP patients are larger, more branched, and more assembled, indicating mature fibrosis.
- The findings suggest that myocardial scarring in MVP is well-established by the time of surgery.

## Abstract

Recent evidence demonstrates that mitral valve prolapse (MVP) increases mechanical stress on the subvalvular apparatus and is linked to regional myocardial fibrosis and life-threatening ventricular arrhythmias. However, current surgical guidelines do not account for the extent of myocardial fibrosis or the severity of leaflet involvement, both key features of arrhythmogenic MVP. To address this gap, we conducted histopathological analysis of endomyocardial biopsies from patients with MVP and regionalized myocardial fibrosis (n = 6) who underwent mitral valve repair. Using digital pathology-based quantitative image analysis (QIA), we found that fibrosis in peri-papillary biopsies exhibited a significantly higher Morphometric Composite Score compared with remote biopsies (5.68 ± 0.69 vs. 3.71 ± 0.49, p = 0.042), reflecting larger, more branched, and more assembled collagen fibers, indicative of a mature and persistent fibrotic phenotype. These findings suggest that myocardial scarring in MVP is well-established by the time of surgery and underscore the potential value of earlier surgical intervention to reduce the risk of arrhythmia and preserve post-operative left ventricular function.

## Linked entities

- **Diseases:** mitral valve prolapse (MONDO:0004910)

## Full-text entities

- **Diseases:** arrhythmia (MESH:D001145), Fibrosis (MESH:D005355), MVP (MESH:D008945), myocardial scarring (MESH:D002921)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12523760/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12523760/full.md

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Source: https://tomesphere.com/paper/PMC12523760