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  Disease summary:

  
  
  
  
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    Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscle characterized by left ventricular hypertrophy (LVH) in the absence of other cardiovascular or systemic conditions (eg, valvular heart diseases or long-standing hypertension).

    
    
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    The histopathologic hallmarks include myocyte hypertrophy, myocardial disarray, and fibrosis.

    
    
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    The prevalence of HCM is 1:500 in the general population, with at least 60% caused by mutation in one of the genes encoding different components of the sarcomere protein (see Molecular Genetics section).

  
  

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  Hereditary basis:

  
  
  
  
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    HCM is inherited in an autosomal dominant manner with age-dependent penetrance and variable expressivity.

  
  

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  Differential diagnosis:

  
  
  
  
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    It is clinically important to distinguish HCM from acquired LVH (eg, physiologic hypertrophy from athletic training, hypertensive heart disease), inherited LVH with multisystem involvement (eg, metabolic cardiomyopathy, cardiac amyloidosis) and syndromes with LVH as a presenting feature. Such diseases with similar cardiac morphologic finding can have different modes of inheritance, natural histories, and therapeutic strategies (Table 25-1).

  
  

Diagnostic Criteria for Hypertrophic Cardiomyopathy

Presence of the following

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  Unexplained LVH with nondilated left ventricular chamber

  
  
  
  
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    Although asymmetric septal hypertrophy is most common, the patterns of hypertrophy are variable and can include concentric and apical hypertrophy.

    
    
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    Most often diagnosed by echocardiography; cardiac MRI may be used to further evaluate left ventricular morphology and to assess for myocardial scar.

    
    
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    Additional findings may include systolic anterior motion (SAM) of the mitral valve with associated left ventricular outflow tract obstruction and mitral regurgitation, mid ventricular obstruction, and diastolic dysfunction.

    
    
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    Less than 10% of patients may develop a burnt-out or end-stage phase characterized by systolic dysfunction, occasionally with regression of LVH and left ventricular dilatation.

  
  

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  Pathognomonic histopathologic features: myocyte disarray, hypertrophy, and cardiac fibrosis

Other findings associated with HCM include

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  Prominent apical impulse or lift

  
  
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  Brisk, occasionally bifid carotid upstroke

  
  
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  A harsh crescendo-decrescendo systolic murmur from dynamic obstruction, best heard at the lower left sternal border and apex, radiating to the axilla and base

  
  
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  Abnormal electrocardiogram (ECG) patterns

  
  
  
  
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    LVH with repolarization abnormalities

    
    
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    Q waves

    
    
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    T-wave inversions

  
  

And the absence of

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  Other cardiovascular conditions or systemic diseases (such as long-standing hypertension, valvular heart diseases, etc) that could account for the degree of LVH seen

Clinical Characteristics

The clinical spectrum of HCM varies widely from individual to individual, even within the same family, ranging from asymptomatic to progressive heart failure and sudden cardiac death. Common symptoms include shortness of breath particularly on exertion, chest pain, palpitations, orthostatic light-headedness, presyncope, and syncope. Diastolic dysfunction is a common finding preceding the development of both hypertrophy and symptoms in sarcomere mutation carriers. Individuals with HCM are at an increased risk for arrhythmias. Atrial fibrillation (AF) is common and associated with increased thromboembolic risk. Sudden cardiac death (SCD) risk is also increased and HCM is the leading cause of SCD in competitive athletes and young individuals in the United States.

Screening

The diagnosis of HCM is suggested by an autosomal dominant pattern of inheritance of unexplained LVH without systemic disease involvement. A family history of the following should be explored in relatives: HCM, LVH, heart failure, cardiac transplantation, SCD or unexplained premature death, conduction disease (eg, need for pacemakers) or arrhythmias, and thromboembolic disease.

In probands, the identification of unexplained LVH is the traditional basis for diagnosing HCM. However, LVH is a sign of established disease only and cannot identify at-risk mutation carriers in the family. It is also nonspecific and cannot differentiate HCM from other forms of cardiac hypertrophy (either genetic or acquired). Incorporating genetic screening of sarcomere genes into clinical evaluation allows confirmation of diagnosis and age-independent identification of relatives at risk for developing HCM. Sarcomere mutations can be identified in approximately 60% of patients with familial HCM and approximately 40% of patients without family history of disease including patients with childhood onset. If a pathogenic mutation is found, confirmatory (predictive) genetic testing can be performed in relatives to identify those definitively at risk for disease. However, sarcomere mutations will not be detected in all individuals with unexplained LVH. A negative result from the genetic testing only eliminates sarcomere gene mutations from the list but does not exclude a genetic cause of LVH. Clinical screening of at-risk relatives may still be appropriate. A diagnostic algorithm for the evaluation of patients presenting with unexplained LVH is summarized in Table 25-2.