Hypertrophic cardiomyopathy (HCM) is usually an autosomal dominant disease of the heart muscle, with an overall prevalence of 1:500 to 1:1000, characterized by a small left ventricular cavity and marked hypertrophy of the myocardium with myofibril disarray.1-8
The basis of HCM has been ascribed to multiple etiologies9,10; however, in 1989, investigators first mapped a genetic mutation for HCM to chromosome 14.11,12 This mutation later was shown to effect the encoding of β-myosin heavy chain protein, which is a major component of the cardiac sarcomere.13,14 Subsequently, hundreds of mutations have been found in HCM patients; most of these mutations involve the myofilaments of the cardiac sarcomere; however, there is increasing awareness of nonsarcomeric mutations as well.15,16 Thus, HCM, in its most common manifestation, is felt to be a disease of the myofilaments, whose alteration in structure and/or function underlies the pathology and pathophysiology in affected individuals.17-27
HCM is a highly heterogeneous disease, with a diverse pathology and clinical course.4-7 Some patients may present with severe limiting symptoms of dyspnea, angina, and syncope, and yet other patients may remain completely asymptomatic throughout life. HCM is the most common cause of sudden cardiac death in young people, including trained athletes.28-34 Yet, the overall prognosis of HCM patients is comparable to that of an age-matched, sex-matched control population.4,35-41
The first anatomic description of HCM was by Teare in 1958,42 when he reported the pathologic findings in eight young patients, seven of whom had died suddenly. He found massive hypertrophy of the ventricular septum with microscopic evidence of myocardial disarray of the individual muscle fibers, which was speculated to be due to either a benign tumor or hamartoma. At the same time, Brock43 reported on patients with functional subvalvular left ventricular outflow tract gradients confirmed by pressure gradients. Braunwald and colleagues, in the 1960s, defined the specific disease process, in which asymmetric septal hypertrophy, myofibril disarray, and a dynamic subvalvular pressure gradient were documented.44,45 This entity was considered to be a primary process with no known cause; however, a genetic connection was suggested when a familial link was shown to be associated with this entity in an autosomal dominant fashion.46
Since these initial descriptions, the disease process has come to be known by many names, including asymmetric septal hypertrophy, idiopathic hypertrophic subaortic stenosis, muscle subaortic stenosis, and hypertrophic obstructive cardiomyopathy. The World Health Organization has designated the term hypertrophic cardiomyopathy (HCM) to describe this unique process of primary muscle hypertrophy, which may exist with or without a dynamic left ventricular outflow tract gradient.47,48
The evolution of echocardiography provided a noninvasive diagnostic tool to identify patients with HCM.49-51 Echocardiography showed that hypertrophy in HCM patients could involve areas other than the ventricular septum and further led to the understanding ...