Etiology and Pathogenesis

Various terms have been used to describe the phenotype of HCM. These include hypertrophic obstructive cardiomyopathy, idiopathic hypertrophic subaortic stenosis, asymmetric septal hypertrophy, and muscular subaortic stenosis—all based on the misconception that dynamic outflow tract obstruction was the key pathologic determinant of the hypertrophy (Fig. 19-2).

Figure 19-2 Anomalies of the left ventricular outflow tract that can mimic valvular aortic stenosis.

It is now accepted that despite the presence or absence of outflow tract obstruction, the principal abnormality is impaired ventricular compliance as a consequence of inappropriate myocardial hypertrophy and diastolic dysfunction. The nonobstructive form of HCM accounts for approximately 75% of cases.

Epidemiology

HCM is inherited in an autosomal-dominant pattern in 50% to 75% of cases. Its prevalence is thought to be 1 per 500 in the general U.S. population and higher in African American individuals. Three age peaks of presentation have been proposed: adolescence, the early 40s, and the early 60s. The clinical presentation of HCM (syncope, sudden cardiac death, severe effort-related chest discomfort, or dyspnea) tends to be most dramatic when HCM presents in adolescence, and more dramatic when the presentation is in the 40s than in the 60s. There is a male predominance in younger patients, whereas there may be an equal or higher prevalence in females in the older population. Clinical presentation with dyspnea, atrial fibrillation, and hypertension is more common in elderly individuals. Echocardiographic differences in two series highlight ovoid LV shape in elderly persons as opposed to reversed septal curvature with a crescent-shaped cavity in persons 40 years or younger. Posterior septal movement, as opposed to systolic anterior motion of the mitral valve, may contribute to higher outflow velocities in elderly individuals. ECG findings of Q waves in the anterior and lateral leads are often seen in the younger group. The genetic basis for HCM is addressed in Chapter 72, Genetics in Cardiovascular Disease.

Clinical Presentation

Some patients with HCM are asymptomatic, and the diagnosis is made after an episode of sudden cardiac arrest. The most common initial symptoms are dyspnea, chest pain, and syncope. Dyspnea is usually exertional and is reported in more than 90% of patients with HCM. Angina occurs in 75% of patients, and MI has been documented in 15% of cases at autopsy. Syncope occurs in approximately 50% of patients. There is no relation between the outflow tract gradient severity and syncopal symptoms except in some circumstances (atrial fibrillation in patients with a significant outflow gradient, see discussion below), suggesting that the most common etiology of syncope in HCM is arrhythmic.

Clinical Syndromes/Variants

Apical hypertrophy is a rare manifestation of HCM, usually presenting in a more benign fashion. The diagnosis is often suggested by very characteristic ECG findings; typically the ECG shows giant negative T waves in the precordial leads. The configuration of the left ventricle is different from that of the usual form of HCM. In patients with apical hypertrophy, an end-diastolic left ventriculogram in the right anterior oblique projection has a characteristic “spadelike” appearance, so called because the LV cavity in this projection resembled the spade in a deck of playing cards. Patients with Costello’s syndrome have HCM and mental and growth retardation, possibly related to advanced parental age and autosomal-dominant inheritance. Distinctive craniofacial findings, resembling those of lysosomal storage disorders, are also present. Other features of this syndrome include acanthosis nigricans, verrucous papillomata of the nose, hyperextensibility of the digits, and soft skin with excess wrinkling over the dorsum of the hands and deep creases on the palms and soles.

Differential Diagnosis

LV hypertrophy (mimicking HCM) may also be present in patients with long-standing systemic hypertension (Fig. 19-3), outflow obstruction secondary to valvular heart disease (e.g., aortic stenosis or coarctation of the aorta), and infiltrative disorders of the myocardium. At times, distinguishing these conditions from HCM clinically, or even by echocardiography, can be very difficult. Tips for making this diagnostic distinction include the following: (1) in patients with aortic stenosis the gradient is fixed, unlike in patients with HCM in whom the gradient is dynamic and may fluctuate with each heartbeat; and (2) the pattern of hypertrophy seen in patients with hypertension is concentric as opposed to the pattern seen in patients with HCM, which is often distinctive, as described later in this chapter.