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Updated: May 22, 2026

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
Distribution of diffuse myocardial fibrosis is uneven and associated with left ventricular function in severe aortic
Erica Holmberg1, Jan Engvall2, Eva Nylander2
1Department of Thoracic and Cardiovascular Surgery, Linkoping University Department of Health Medicine and Caring Sciences, Linköping, Sweden erica.holmberg@liu.se.
Background:
Aortic stenosis (AS) leads to left ventricular (LV) remodelling and fibrosis. Myocardial fibrosis can be focal and irreversible, associated with poor prognosis, or diffuse and potentially reversible after surgery. Cardiac magnetic resonance imaging (CMR) shows promise in quantifying diffuse myocardial fibrosis (DMF), but methods vary in precision. The aim of this study was to investigate the presence and distribution of DMF from myocardial biopsies and CMR tissue characteristics in severe AS. Secondarily, explore the association between DMF and LV function.
Methods:
Forty-three patients with severe AS underwent CMR and transthoracic echocardiography within 1 week before surgical aortic valve replacement. CMR included balanced steady-state free-precession cine images, T1 relaxometry with Modified Look-Locker Inversion recovery and extracellular volume calculations. Endomyocardial biopsies were sampled.
Results:
Histological analysis of 192 biopsies showed a median LV collagen volume fraction (CVF) of 19%, peaking in segment 1, according to the segment model recommended by the American Heart Association (AHA). There were significant moderate correlations between CVF and extracellular volume in AHA segments 1 (r² = 0.54, p<0.01) and 16 (r² = 0.44, p=0.03), where the DMF had the highest prevalence. Functional assessments demonstrated correlations between CVF and global circumferential and radial strain (r2 0.31, p=0.04 respectively r2-0.33, p=0.03), as well as LV ejection fraction (r2-0.34, p=0.03). T1 relaxation time correlated with GLS (r2 0.42, p<0.01), mitral annular plane systolic excursion (r2-0.39, p=0.01) and mean S' LV (r2-0.45, p<0.01) from transthoracic echocardiography.
Conclusion:
CVF varied across LV segments and was significantly highest at the base of the heart, suggesting the start location for fibrosis. Systolic functional data correlated with CVF and T1 relaxation time.
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