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Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease
A M Varnava1, P M Elliott, S Sharma
1Department of Cardiovascular Pathology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. avarnava@sghms.ac.uk
Insights
In hypertrophic cardiomyopathy, myocyte disarray is linked to genetic factors, while fibrosis and small vessel disease are separate issues influenced by heart size and sex.
Area of Science:
- Cardiovascular Pathology
- Cardiac Histology
- Genetic Cardiomyopathies
Background:
- Hypertrophic cardiomyopathy (HCM) is a primary genetic heart muscle disease.
- Histological abnormalities like myocyte disarray, fibrosis, and small vessel disease are common in HCM.
- The interrelationships between these pathological features and their clinical impact require further quantitative assessment.
Purpose of the Study:
- To quantitatively assess the relationships between myocyte disarray, fibrosis, and small vessel disease in hypertrophic cardiomyopathy.
- To explore how these features correlate with clinical and pathological parameters in HCM patients.
Main Methods:
- Macroscopic and histological examination of 19 cardiac segments from 72 patients with severe HCM.
- Quantification of myocyte disarray, fibrosis, and small vessel disease.
- Assessment of heart weight, wall thickness, scarring, atrial dilatation, and mitral valve impact lesions.
Main Results:
- Within individual hearts, hypertrophy correlated with fibrosis and disarray.
- Overall heart weight showed weak correlations with fibrosis and small vessel disease, but not disarray.
- Myocyte disarray was more pronounced in hearts with mild hypertrophy and without mitral valve impact lesions.
- Fibrosis was influenced by sex, but no direct relationship was found between disarray, fibrosis, and small vessel disease.
Conclusions:
- Myocyte disarray in HCM likely stems from direct effects of mutated sarcomeric proteins.
- Fibrosis and small vessel disease appear to be secondary processes, independent of myocyte disarray.
- These secondary changes are modulated by factors including left ventricular mass and patient sex.
Objective:
To make a quantitative assessment of the relation between disarray, fibrosis, and small vessel disease in hypertrophic cardiomyopathy.
Design:
Detailed macroscopic and histological examination at 19 segments of the left and right ventricle and the left atrial free wall.
Patients:
72 patients with hypertrophic cardiomyopathy who had suffered sudden death or progression to end stage cardiac failure (resulting in death or heart transplantation).
Main Outcome Measures:
The presence of scarring, atrial dilatation, and a mitral valve impact lesion were noted, and heart weight, wall thickness, per cent disarray, per cent fibrosis, and per cent small vessel disease quantitated for each heart.
Results:
Within an individual heart the magnitude of hypertrophy correlated with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002). Overall, however, total heart weight related weakly but significantly to fibrosis (r = 0.4, p = 0.0001) and small vessel disease (r = 0.3, p = 0.03), but not to disarray. Disarray was greater in hearts with mild left ventricular hypertrophy (maximum wall thickness < 20 mm) and preserved systolic function (60.9 (26)% v 43 (20.4)% respectively, p = 0.02) and hearts without a mitral valve impact lesion (26.3% v 18.9%, p = 0.04), but was uninfluenced by sex. Fibrosis was influenced by sex (7% in male patients and 4% in female, p = 0.04), but not by the presence of an impact lesion. No relation was found between disarray, fibrosis, and small vessel disease.
Conclusions:
Myocyte disarray is probably a direct response to functional or structural abnormalities of the mutated sarcomeric protein, while fibrosis and small vessel disease are secondary phenomena unrelated to disarray, but modified by factors such as left ventricular mass, sex, and perhaps local autocrine factors.