Specificity of light and electron microscopic features of hypertrophic obstructive and nonobstructive cardiomyopathy. Qualitative, quantitative and etiologic aspects

A review is presented of the histologic and ultrastructural abnormalities found in the hearts of patients with hypertrophic cardiomyopathy. Evidence is presented to show that myocardial fiber disarray is found in hypertrophic cardiomyopathy as well as in other conditions; however, in the latter it seldom involves more than 5% of the myocytes in transverse sections of ventricular septum. A new theory of morphogenesis is proposed to account for the asymmetric cardiac hypertrophy that characterizes hypertrophic cardiomyopathy. This theory is summarized as follows: (1) hypercontractility is the underlying abnormality affecting cardiac myocytes; (2) this hypercontractility is present during embryonic development and constitutes the stimulus to the inappropriate increase in cardiac mass that takes place in hypertrophic cardiomyopathy; (3) during embryonic development this stimulus results in increased mitotic division (i.e. hyperplasia) rather than in increased size of individual myocytes (i.e. hypertrophy); (4) hyperplasia is preferentially increased in the ventricular septum (perhaps because of the mechanical forces exerted by left and right ventricular contraction on the ventricular septum), thus exaggerating the asymmetric growth that occurs normally in this area during prenatal development; (5) after birth, the septal asymmetry does not regress in patients with hypertrophic cardiomyopathy, as it does in normal individuals, because it is complicated by hyperplasia (i.e. increased numbers of myocytes are already present in the ventricular septum); (6) the prenatal phase of hyperplasia is followed by a postnatal phase of gradual, progressive hypertrophy in which myocytes enlarge, septal hypertrophy becomes exaggerated, and clinical symptoms eventually develop.