Hypertrophic cardiomyopathy, or HCM, is a disease of the myocardium (the muscle of the heart) in which a portion of the myocardium is hypertrophied (thickened) without any obvious cause. Though perhaps most famous as a leading cause of sudden cardiac death in young athletes. The occurrence of hypertrophic cardiomyopathy is a significant cause of sudden unexpected cardiac death in any age group and as a cause of disabling cardiac symptoms.
A cardiomyopathy is a disease that primarily affects the muscle of the heart. With hypertrophic cardiomyopathy (HCM), the normal alignment of muscle cells is disrupted, a phenomenon known as myocardial disarray. HCM also causes disruptions of the electrical functions of the heart. HCM is believed to be due to a mutation in one of many genes that results in a mutated myosin heavy chain, one of the components of the myocyte (the muscle cell of the heart). Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of blood from the left ventricle of the heart, HCM can be defined as obstructive or non-obstructive. The obstructive variant of HCM, Hypertrophic obstructive cardiomyopathy (HOCM) has also historically been known as idiopathic hypertrophic subaortic stenosis (IHSS) and asymmetric septal hypertrophy (ASH). Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy, first described in individuals of Japanese descent.
While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The incidence of HCM is about 0.2% to 0.5% of the general population.
Genetics
Hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for one of the sarcomere proteins including beta-cardiac myosin heavy chain (the first gene identified), cardiac actin, cardiac troponin T, alpha-tropomyosin, cardiac troponin I, cardiac myosin-binding protein C, and the myosin light chains. Currently there are more than 400 mutations in these genes. Approximately 45% of these mutations occur in the β myosin heavy chain gene on chromosome 14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C gene. The prognosis is variable, based on the gene mutation. In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation of the gene that produces the β-myosin heavy chain.
An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes.
Anatomic characteristics
Individuals with HCM have some degree of left ventricular hypertrophy. Usually this is an asymmetric hypertrophy, involving the inter-ventricular septum, and is known as asymmetric septal hypertrophy (ASH). This is in contrast to the concentric hypertrophy seen in aortic stenosis or hypertension. About two-thirds of individuals with HCM have asymmetric septal hypertrophy.
About 25% of individuals with HCM demonstrate an obstruction to the outflow of blood from the left ventricle during rest. In other individuals obstruction only occurs under certain conditions. This is known as dynamic outflow obstruction, because the degree of obstruction is variable and is dependent on the amount of blood in the ventricle immediately before ventricle systole (contraction).
