Stanford Cardiac Arrhythmia Service

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is the accepted term used for a heart condition in which there is thickening of the main pumping chamber of the heart, called the left ventricle.  This condition is felt generally to be genetic in origin, but not all individuals have a clear family history that is apparent. 

The prevalence of the condition is estimated to be one in 500, or 0.2%.  This frequency makes hypertrophic cardiomyopathy the most common genetic cardiovascular disorder.  The frequency of hypertrophic cardiomyopathy has been reported throughout the world and is felt to affect all major ethnic groups.  Although the frequency has been reported at this level, a large percentage of patients have not received the diagnosis.

Genetics of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is inherited in a manner in which each affected patient has at least one parent with the trait.  This form of inheritance is called Mendelian simple dominance.  In most of these patients, only one gene is felt to be responsible for inheritance of hypertrophic cardiomyopathy.  The approximately ten genes that have been identified to date involve specific proteins within the heart muscle structure.  This explains why the major way in which hypertrophic cardiomyopathy is expressed or displayed is in the thickness of the wall itself.  In the figure, you see an example of some of the proteins responsible for heart muscle contraction within a structure called the cardiac sarcomere.  This structure has thick and thin filaments which are responsible for contractions of the heart muscle. 

Three of the major genes responsible for hypertrophic cardiomyopathy affect a specific part of the sarcomere.  These are responsible for the steps in the heart contraction process.  These include beta-myosin heavy chain, cardiac troponin T, and myosin-binding protein C.  There are less common gene abnormalities, such as involving cardiac troponin I, myosin light chains, [–pitin], alpha-tropomyosin, alpha-actin, and alpha-myosin heavy chain.  In most cases, the protein that is affected in hypertrophic cardiomyopathy is only different from the normal molecule by one very small part called a single amino acid.

Echocardiography

In nearly all patients diagnosed with hypertrophic cardiomyopathy, the echocardiogram shows increased wall thickness.  The degree of wall thickness ranges greatly from being relatively minimal (13-15 mm) to massive (30 mm or greater).  The normal range, depending on the echocardiographic laboratory, is usually up to a maximum of 11 to12 mm.  Although thickness of the heart is used as the primary method of making this diagnosis, there are other causes of thickening of the ventricle.  The most common cause is elevated blood pressure, or hypertension.  Individuals with hypertension may even develop a relatively severe degree of thickening.  Therefore, if the patient is found to have thickening of the wall, assessment of blood pressure is important to determine whether the patient has hypertension or high blood pressure.  Individuals with thickening of the wall due to high blood pressure are not felt to have hypertrophic cardiomyopathy, despite the increased wall thickness.  This is because the high blood pressure itself causes the wall thickening, rather than there being an inherited cause.  In individuals with thickening of the heart due to high blood pressure, there is not felt to be an increased risk of other heart abnormalities, such as serious heart rhythm problems such as ventricular tachycardia. 

Genetic Testing

Genetic testing is able to identify the abnormalities which are currently known to be identified in patients with hypertrophic cardiomyopathy.  More and more gene abnormalities are being discovered.  Approximately 60 to 70% of patients with known hypertrophic cardiomyopathy are felt to have a currently identifiable gene abnormality.  These can be identified using the commercially available tests.  The primary benefit of identifying genetic abnormality is to be able to help family members determine if they also have hypertrophic cardiomyopathy, or the gene responsible for it.  If the individual has a gene identified, but the family member does not, that family member will not move to be further screened for hypertrophic cardiomyopathy in the future. 

Screening Methods Other Than Genetic Analysis

The standard echocardiogram is the most commonly used technique to identify the wall thickness for hypertrophic cardiomyopathy.  Because hypertrophic cardiomyopathy may develop as the patient ages, it is important that echocardiography be repeated through the patient’s lifetime in order to identify whether the individual has hypertrophic cardiomyopathy, once a family member has this identified. 

Frequently, patients are discovered to have hypertrophic cardiomyopathy because they develop symptoms which may range from racing heart (palpitations), dizziness, or passing out.  They also may be found to have had heart rhythm problems such as atrial fibrillation or ventricular tachycardia.  Other individuals may have been told of an abnormal electrocardiogram (ECG) and that is the reason why they have an echocardiogram.

Hypertrophic cardiomyopathy may be detected because of a heart murmur on routine physical examination or pre-participation sports examination.  Most individuals with hypertrophic cardiomyopathy do not have a heart murmur, however. 

Screening of Relatives of Patients with Hypertrophic Cardiomyopathy

Each patient with hypertrophic cardiomyopathy has a parent carrying the gene for hypertrophic cardiomyopathy even if the parent did not have symptoms or the diagnosis made. One of the patient’s grandparents also has the gene.  There is a 50% chance that a patient’s siblings or children will have the gene. 

If the patient has genetic testing and a gene if identified, the family members just need to have genetic testing and no other testing is required unless a gene is identified in those individuals.  If the patient has genetic testing but does not have a gene identified, the patient’s parent, siblings, and children should have regular electrocardiogram and echocardiogram testing. The current recommendations are that children have both these tests annually until puberty or age 18.  After age 18, these tests may be taken every 5 years.

Ventricular Tachycardia and Sudden Cardiac Death in Hypertrophic Cardiomyopathy

The major cause of death in patients with hypertrophic cardiomyopathy may be serious life-threatening arrhythmias called ventricular tachycardia or ventricular fibrillation.  It should be emphasized that most patients with hypertrophic cardiomyopathy will never have a serious or life-threatening ventricular arrhythmia.  In fact, many studies indicate that the overall survival of patients with hypertrophic cardiomyopathy approximates that of the general population.

Why, then, are we concerned about ventricular tachycardia and hypertrophic cardiomyopathy? There is a subset of patients with hypertrophic cardiomyopathy in whom ventricular arrhythmias are the major cause of death.  In fact, in many families, the first evidence of hypertrophic cardiomyopathy is the existence of a death in an individual due to hypertrophic cardiomyopathy. 

Once patients are given the diagnosis of hypertrophic cardiomyopathy, how do we determine if they are at increased risk of these serious ventricular arrhythmias?  In addition to a complete family history, physical examination and history, there are number of tests that are usually performed:  exercise stress testing, ECG monitoring for 24 hours or more (often called Holter or ambulatory ECG monitoring).  There are a number of criteria that are used:  History of prior cardiac arrest (ventricular tachycardia or ventricular fibrillation requiring an electrical shock to restore normal heart rhythm), nonsustained ventricular tachycardia (a series of fast heart beats from the lower heart chamber) on ECG monitoring, episodes of loss of consciousness (without clear explanation), decrease in blood pressure or failure of blood pressure to rise during exercise testing, massive heart wall thickness (30mm is often used but some physicians may select another cut-off value), family history of sudden death.   If patients have one or more of these criteria, physicians will discuss with patients the option of a special device called an implantable cardioverter defibrillator (ICD) and determine if this treatment is right for the patient.

History of prior cardiac arrest nonsustained ventricular tachycardia episodes of loss of consciousness decrease in blood pressure or failure of blood pressure to rise during exercise testing, massive heart wall thickness family history of sudden death.

Atrial Fibrillation in Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy are much more likely to develop atrial fibrillation than the general public. Patients with atrial fibrillation may develop symptoms of shortness of breath, dizziness, chest pain, and racing heart.  The diagnosis is made with electrocardiogram (ECG) or ECG monitoring.  Patients will frequently need to be on medications to slow the heart rate or restore normal rhythm.

 In studies of patients with hypertrophic cardiomyopathy with stroke nearly 90% of patients had atrial fibrillation. The risk of stroke appears to be less in patients with atrial fibrillation and hypertrophic cardiomyopathy having warfarin (Coumadin) anticoagulation.

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