Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure

Elles M. Screever, Thomas M. Gorter, Tineke P. Willems, Joseph Pierre Aboumsallem, Navin Suthahar, Belend Mahmoud, Dirk J. van Veldhuisen, Rudolf A. de Boer, Wouter C. Meijers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Aims: Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. Methods and results: In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan–Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 μg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). Conclusion: This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

Original languageEnglish
Article number410
JournalBiomolecules
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2023

Bibliographical note

Funding Information:
This work was supported by grants from the Dutch Heart Foundation (Dekker grant 03-005-2021-T005) and the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10 of the University Medical Center Groningen, both to Wouter C. Meijers.

Publisher Copyright:
© 2023 by the authors.

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