The diagnosis of hypertrophic cardiomyopathy

Although the pathology of hypertrophic cardiomyopathy (HCM) was first described by French pathologists in the mid 19th century, it remained for the virtually simultaneous reports of Brock and Teare in England some 43 years ago to bring modern attention to this fascinating entity.1 2 Subsequent to these surgical1 and pathological2 observations, there has been an almost exponential growth in the number of research reports and in our knowledge of HCM, and a number of extensive reviews have been published.3-9 HCM was initially thought to be relatively rare, but it is now recognised to be an important cause of morbidity and mortality in people of all ages. In tertiary referral populations the annual mortality is 3–4% per annum (higher in the young) and 1–2% per annum in non-referred populations. It occurs in 1 in 500 live births, making it as common as cystic fibrosis, and is the most common cause of sudden death during athletic endeavour in young people. The diagnosis of HCM is therefore of great importance, particularly in the young where sudden death is such a risk. More recently, the results of molecular genetic studies have resulted in a quantum leap in our basic knowledge and understanding of the Mendelian dominant inheritance of HCM and have far reaching prognostic and clinical implications. HCM is now described as a heterogeneous disease of the sarcomere in that more than 150 different mutations in 10 different sarcomeric proteins have been shown to cause HCM8 (table 1). These molecular genetic studies are already having important clinical implications in that some mutations carry a benign prognosis, whereas others, possibly interacting with various growth factors, have increased penetrance, early onset of manifestations, and a bad prognosis, thus explaining the malignant family history noted in some instances. Because of the time …