Luke Cunningham, MD and Kumudha Ramasubbu, MD, FACC

1. What is hypertrophic cardiomyopathy?

    Hypertrophic cardiomyopathy (HCM) is a primary disorder of the cardiac muscle characterized by inappropriate myocardial hypertrophy of a nondilated left ventricle (LV) in the absence of a cardiovascular or systemic disease (i.e., aortic stenosis or systemic hypertension). Historically, HCM has been known by a confusing array of names, such as idiopathic hypertrophic subaortic stenosis (IHSS), muscular subaortic stenosis, and hypertrophic obstructive cardiomyopathy (HOCM). Currently, hypertrophic cardiomyopathy is the preferred term.

2. What is the prevalence of HCM?

    The reported prevalence of HCM from epidemiologic studies is about 1:500 in the general population (0.2%). HCM affects men and women equally and occurs in many races and countries.

3. What are the genetic mutations that cause HCM, and how are they transmitted?

    Thus far, more than 400 mutations in 11 genes have been identified that can cause HCM. These genes encode for cardiac sarcomere proteins that serve contractile, structural, and regulatory functions. They are cardiac troponin T, cardiac troponin I, myosin regulatory light chain, myosin essential light chain, cardiac myosin-binding protein C, α- and β-cardiac myosin heavy chain, cardiac α actin, α tropomyosin, titin, and muscle LIM protein (MLP). Mutations in cardiac myosin-binding protein C and β-cardiac myosin heavy chain are the most common and account for 82% of all mutations. HCM is inherited as an autosomal dominant trait; therefore, patients with HCM have a 50% chance of transmitting the disease to each of their offspring.

4. Who should be screened for HCM?

    Patients with known HCM mutations, but without evidence of disease, and first-degree relatives of patients with HCM should be screened. Screening is performed primarily with history, physical examination, 12-lead electrocardiogram (ECG), and two-dimensional echocardiography. Traditionally, screening was performed on a 12- to 18-month basis, usually beginning by age 12 until age 18 to 21. However, it is now recognized that development of the HCM phenotype uncommonly can occur later in adulthood. Therefore, the current recommendation is to extend clinical surveillance into adulthood at about 5-year intervals or to undergo genetic testing (Table 27-1).

5. Who should undergo genetic testing?

    Genetic testing, which is not commercially available, has become recognized as an important aspect in the evaluation of HCM. It is strongly recommended that patients diagnosed with HCM be evaluated by a genetics specialist. In an index patient, genetic testing is also recommended in order to identify the risk in first-degree family members of developing HCM. First-degree relatives of patients with HCM should undergo the previously discussed clinical screening, with or without genetic testing based on genetic counseling. However, genetic testing is not helpful in first-degree family members of an HCM patient without identifiable pathologic mutation.

6. What are the histologic characteristics of HCM?

    The histology of HCM is characterized by hypertrophy of cardiac myocytes and myocardial fiber disarray. The abnormal myocytes contain bizarrely shaped nuclei and are arranged in disorganized patterns. The volume of the interstitial collagen matrix is greatly increased, and the arrangement of the matrix components is also disorganized. Myocardial disarray is seen in substantial portions of hypertrophied and nonhypertrophied LV myocardium. Almost all HCM patients have some degree of disarray, and in the majority, at least 5% of the myocardium is involved.

7. What are the common types of HCM?

    The distribution and severity of LV hypertrophy in patients with HCM can vary greatly. Even first-degree relatives, with the same genetic mutation, usually show different patterns of hypertrophy. Various patterns of LV hypertrophy have been reported. The most common site of hypertrophy is the anterior interventricular septum (Fig. 27-1), which is seen in more than 80% of HCM patients and is known as asymmetrical septal hypertrophy (ASH). Concentric LV hypertrophy, with maximal thickening at the level of the papillary muscles, is seen in 8% to 10% of patients with HCM. A variant with primary involvement of the apex (apical HCM) is common in Japan and rare in the U.S. (less than 2%) and is characterized by spadelike deformity of the LV.

8. What are the most common symptoms in patients with HCM?

    Most patients with HCM have no or only minor symptoms and often are diagnosed during family screening. The most common symptoms are as follows:

9. How is HCM differentiated from athlete’s heart?

    Long-term athletic training can lead to cardiac hypertrophy, known as athlete’s heart. This clinically benign physiologic condition must be differentiated from HCM, because HCM is the most common cause of sudden death in competitive athletes. Clinical parameters that support the diagnosis of HCM instead of athlete’s heart are asymmetric hypertrophy greater than 16 mm, LV end-diastolic dimension less than 45 mm, enlarged left atrium, impaired LV relaxation on Doppler mitral valve inflow parameters and tissue Doppler echocardiography, absent response to deconditioning (e.g., hypertrophy does not regress with absence of exercise), family history of HCM, and sarcomeric protein mutation identified by genetic testing. These parameters are summarized in Table 27-2.