Related Experiment Video
Updated: Jul 27, 2026

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
Influence of collagen network on left ventricular systolic and diastolic function in aortic valve disease
B Villari1, S E Campbell, O M Hess
1Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Insights
In aortic valve disease, altered collagen structure, not just increased amount, impacts heart function. Changes in the heart
Area of Science:
- Cardiovascular Research
- Cardiac Pathology
- Biomedical Engineering
Background:
- Myocardial fibrosis increases in aortic valve disease.
- Collagen network changes and their functional impact are not well understood.
Purpose of the Study:
- To investigate the relationship between left ventricular structure and function in patients with aortic valve disease.
- To define the role of collagen alterations in the progression of cardiac dysfunction.
Main Methods:
- Assessed left ventricular endomyocardial biopsies from 32 patients with aortic valve disease.
- Quantified collagen volume, fiber architecture, and myocyte characteristics.
- Evaluated systolic and diastolic function using cineangiography and pressure measurements.
Main Results:
- Increased muscle fiber diameter observed across all patient groups.
- Systolic function (ejection fraction) was impaired in groups with architectural collagen changes.
- Diastolic relaxation was prolonged, and myocardial stiffness increased in advanced disease stages.
Conclusions:
- Collagen architecture, not just volume, is crucial for maintaining normal systolic and diastolic function in aortic valve disease.
- Isolated increases in collagen volume without architectural changes did not affect cardiac function.
Objectives:
The purpose of this study was to evaluate left ventricular structure-function interplay in aortic valve disease.
Background:
An increase in myocardial fibrosis has been demonstrated in aortic valve disease, but changes in the collagen network and their effect on ventricular function have not been defined.
Methods:
Left ventricular structure was assessed from left ventricular endomyocardial biopsy specimens obtained in 32 patients with aortic valve disease (aortic stenosis in 25, aortic regurgitation in 7). Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching), endocardial fibrosis, muscle fiber diameter and volume fraction of myofibrils were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from six donor hearts before transplantation. Eleven other patients with normal left ventricular function served as hemodynamic status control subjects. Left ventricular biplane cineangiography and high fidelity pressure measurements were carried out in all patients. Systolic function was assessed from ejection fraction. Diastolic function was evaluated by the time constant of relaxation, early and late peak filling rates and the constant of passive myocardial stiffness. Patients were assigned to three groups according to increasing severity of nonmyocyte tissue alterations. Group 1 comprised 10 patients with elevated total collagen volume fraction. Group 2 comprised 6 patients with normal total collagen volume fraction and the presence of increased cross-hatching or endocardial fibrosis, or both. Group 3 comprised 16 patients with elevated total collagen volume fraction and the presence of cross-hatching or endocardial fibrosis, or both.
Results:
Muscle fiber diameter was increased in the three groups with aortic valve disease, whereas the volume fraction of myofibrils was comparable in all four study groups. Ejection fraction was depressed in groups 2 and 3 compared with the control group. The time constant of relaxation was prolonged in the three groups with aortic valve disease. No differences in early and late peak filling rate were observed in the four study groups, but the constant of myocardial stiffness increased in groups 2 and 3.
Conclusions:
In aortic valve disease, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered.
Related Concept Videos
Mitral Valve Prolapse I: Introduction
Mitral Stenosis I: Introduction
Aortic Regurgitation I: Introduction
Aortic Regurgitation II: Clinical Features and Diagnostic Tests
Aortic Regurgitation III: Medical Management
Heart Failure II: Pathophysiology

