Although the pathology of HCM was described by two French pathologists in the mid 19th century 1 2 and by a German pathologist in the early 20th century, 3 it remained for the virtually simultaneous reports of Brock 4 and Teare, 5 some 37 years ago, to bring modern attention to this fascinating entity. Subsequent to these surgical 4 and pathological 5 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. 6 7 8 9 10 11 The growth in our knowledge of HCM parallels the development of various investigative techniques available to cardiology. Thus, the 1960s and 1970s were the clinical, 12 13 14 15 16 hemodynamic, 17 18 19 20 21 22 23 24 25 26 27 28 29 and angiographic 30 31 32 33 era that focused mainly on obstructive HCM. The 1970s through the 1990s saw the various imaging modalities (echo-Doppler, 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 nuclear, 49 50 51 52 53 54 magnetic resonance, 55 56 57 58 and positron emission tomography 59 60) enhance our understanding of the systolic and diastolic abnormalities as well as the significance of myocardial ischemia in HCM. At the same time, electrophysiological techniques defined the spectrum of atrial and ventricular arrhythmias that are such an important feature of this disease. 61 62 63 64 65

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. 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 HCM is now described as a heterogeneous disease of the sarcomere, 77 78 in that at least 34 missense mutations have been described in the β-myosin heavy chain gene (chromosome 14q11-q12), 66 67 68 69 70 71 72 75 76 7 mutations have been described in cardiac troponin-T (chromosome 1), 74 77 79 and 2 mutations in α-tropomyosin (chromosome 15q2). 77 78 Another locus has been found on chromosome 11p13-q13, 73 and familial HCM with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. 80 The hypertrophy in HCM may be compensatory in response to the abnormalities induced by these mutations. This belief is supported by the upregulation of genes commonly observed in compensatory hypertrophy, ie, atrial and brain natriuretic peptides and angiotensin-converting enzyme. 81 82 83 84 85 86 These molecular genetic studies are already having important clinical implications in that some mutations carry a benign prognosis, 69 77 whereas others, possibly interacting with angiotensin-converting enzyme genotypes, 85 86 have increased penetrance, early onset of manifestations, and a bad prognosis, 69 77 79 thus explaining the malignant family history noted by some authors. 87