HYPERTROPHIC CARDIOMYOPATHY - PATHOLOGY AND PATHOGENESIS

Genes on five loci on separate chromosomes are responsible for a familial disease in which all or part of the ventricular muscle undergoes thickening with a histological picture of irregular hypertrophy and disorganized arrangement of myocytes (disarray), The three genes identified so far encode for beta heavy chain myosin (chromosome 14), troponin T (chromosome 1) and alpha tropomyosin (chromosome 15). It is postulated that the phenotype within the heart is produced by abnormal myofibril formation and alignment leading to an abnormal cell shape and, thus, disarray, While all the myocytes carry the gene, the regional selectivity of the hypertrophy is unexplained, The phenotypic expression of the disease within affected members of one family, all of whom are heterozygous for the same gene abnormality, is very varied. Asymptomatic carriers are common, and new mutations do not account for most apparently isolated cases. The phenotypic expression of the disease was studied in 75 hearts, The increase in total heart weight ranged from near normal to over 800 g, Ventricular involvement was diffuse and symmetric in 42%. The commonest asymmetric form involved the anteroseptal region (31%) but sporadic cases involved only the posterior or lateral wall, A minority of cases (9.5%) did not show macroscopic wall thickening. Fibrosis is often associated with dysplastic changes in the media of small intramyocardial arteries and may lead to the ventricular wall simulating a dilated cardiomyopathy. A subaortic patch of endocardial thickening on the ventricular septum due to contact with the anterior cusp of the mitral valve was found in a third of cases. The variation in the macroscopic appearances of the disease is so great that extensive histological examination is required in cases of sudden death to confirm or exclude the diagnosis. Exaggerated responses to hypertension or prolonged physical training may produce left ventricular hypertrophy closely mimicking hypertrophic cardiomyopathy but disarray is absent. Such cases may die suddenly. High circulating levels of angiotensin are thought to be responsible, either because of renal disease or due to polymorphisms in the angiotensin converting enzyme gene.