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Updated: Sep 5, 2025

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
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Impact of Myocardial Fibrosis on Cardiovascular Structure, Function and Functional Status in Heart Failure with

Gavin A Lewis1,2, Anna Rosala-Hallas3, Susanna Dodd4

  • 1Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

Journal of Cardiovascular Translational Research
|July 5, 2022
PubMed

Insights

Antifibrotic therapy improved heart failure symptoms, but regression of myocardial fibrosis did not significantly improve left ventricular ejection fraction (LVEF) in patients with heart failure with preserved ejection fraction (HFpEF).

Area of Science:

  • Cardiology
  • Biomedical Engineering
  • Translational Medicine

Background:

  • Myocardial fibrosis is linked to poor outcomes in heart failure with preserved ejection fraction (HFpEF).
  • The precise mechanisms by which fibrosis impacts cardiovascular function in HFpEF remain incompletely understood.

Purpose of the Study:

  • To investigate if regression of myocardial fibrosis mediates improvements in cardiovascular function and functional status after antifibrotic therapy.
  • To analyze the causal mediation effects of fibrosis components on left ventricular ejection fraction (LVEF) in HFpEF patients.

Main Methods:

  • Mediation analyses were conducted on data from the Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction (PIROUETTE) trial.
  • Cardiovascular magnetic resonance extracellular volume (ECV) was used to measure myocardial fibrosis.

Main Results:

  • Regression of myocardial fibrosis correlated with enhanced 6-minute walk test performance and KCCQ clinical summary scores.
  • Left ventricular ejection fraction (LVEF) showed a treatment effect, increasing post-therapy.
  • No significant causal mediation effects were found for myocardial ECV, extracellular matrix volume, or cellular volume on LVEF.

Conclusions:

  • While antifibrotic therapy shows benefits in HFpEF functional status, myocardial fibrosis regression does not appear to be the primary mediator of LVEF improvement.
  • Further research is needed to elucidate the mechanisms linking fibrosis to adverse outcomes and therapeutic responses in HFpEF.

Keywords:
Heart failure with preserved ejection fractionMagnetic resonance imaging (MRI)Mediation analysisMyocardial fibrosis

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