Management of symptoms in hypertrophic cardiomyopathy.

In 1957, Brock1 made the distinction between congenital subaortic stenosis characterized by a fibrous ridge and “functional subvalvar stenosis” resulting from “muscular hypertrophy,” describing 3 patients with the latter. Brock initially attributed the hypertrophy and resultant outflow obstruction to systemic hypertension, a conclusion he withdrew in a 1959 publication.2 Between these 2 publications, Teare3 described asymmetrical septal hypertrophy in 8 autopsies (from a series of 16 000!). Remarkably, he identified myocyte disarray, proclivity for sudden death during exertion, and occurrence of stroke in association with atrial fibrillation as features of the disease. Quantitative definition of asymmetrical septal hypertrophy as septal to posterior wall thickness ratio 1.3 was introduced in 1961.4 The discovery that the left ventricular outflow tract (LVOT) gradient was created by systolic anterior motion (SAM) of the mitral valve was made from analysis of cineangiograms a year later.5 Soon thereafter, it was recognized that diverse patterns of hypertrophy existed. In the early 1970s, investigators came to realize that, even among patients with asymmetrical septal hypertrophy, obstruction to left ventricular (LV) outflow at rest was present in only a minority.6 The recognition that an impediment to LV inflow (eg, diastolic dysfunction) might be at least as important as any obstruction to outflow came with the observation that LV end-diastolic pressure (LVEDP) was elevated while LV end-diastolic volume (LVEDV) was normal or low in many patients with hypertrophic cardiomyopathy (HCM).7 The genetic basis of the disease was demonstrated in 1990.8 Half a century after the descriptions of Brock and Teare, HCM is now understood to be a disease characterized by idiopathic hypertrophy of the left (and occasionally right) ventricle. Although the disease is often inherited in an autosomal dominant pattern, there are many patients without any relatives who are known to have the disease. The prevalence of the disorder is estimated to be 0.2%.9 There are diverse patterns of hypertrophy, including asymmetrical septal hypertrophy with or without a LVOT gradient, midventricular hypertrophy with or without an associated gradient, apical hypertrophy, LV free wall hypertrophy, and concentric hypertrophy, the latter mimicking that seen in patients with systemic hypertension. A subset of patients with HCM has hypertrophic obstructive cardiomyopathy (HOCM), characterized by asymmetrical symmetrical hypertrophy, SAM, an LVOT gradient, and varying degrees of mitral regurgitation. The degree of LVOT obstruction is generally variable. In some patients, it is always present at rest; in others (HOCM with “latent” or “provocable” obstruction), it is absent at rest but provoked by stimuli such as exercise, Valsalva maneuver, and postextrasystolic potentiation. When patients with provocable obstruction are included, the subset with HOCM constitutes the majority of patients referred to a specialty center.10 As originally suspected by Brock, systemic hypertension may cause a condition that mimics all of the hemodynamic features, both systolic and diastolic, of HOCM.