Hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. When multiple members of a family have the condition, it is known as familial hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy also occurs in people with no family history; these cases are considered nonfamilial hypertrophic cardiomyopathy.

In familial hypertrophic cardiomyopathy, cardiac thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Familial hypertrophic cardiomyopathy often begins in adolescence or young adulthood, although it can develop at any time throughout life.

The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.

While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.

Nonfamilial hypertrophic cardiomyopathy tends to be milder. This form typically begins later in life than familial hypertrophic cardiomyopathy, and affected individuals have a lower risk of serious cardiac events and sudden death than people with the familial form.

Variants (also known as mutations) in one of several genes can cause familial hypertrophic cardiomyopathy; the most commonly involved genes are MYH7, MYBPC3, TNNT2, and TNNI3. Other genes may also be involved in this condition, including some that have not been identified.

The proteins produced from the genes associated with familial hypertrophic cardiomyopathy play important roles in tensing (contraction) of the heart muscle by forming muscle cell structures called sarcomeres. Sarcomeres, which are the basic units of muscle contraction, are made up of thick and thin protein filaments. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body.

The protein produced from the MYH7 gene, called cardiac beta (β)-myosin heavy chain, is the major component of the thick filament in sarcomeres. The protein produced from the MYBPC3 gene, cardiac myosin binding protein C, associates with the thick filament, providing structural support and helping to regulate muscle contractions.

The TNNT2 and TNNI3 genes provide instructions for making cardiac troponin T and cardiac troponin I, respectively, which are two of the three proteins that make up the troponin protein complex found in cardiac muscle cells. The troponin complex associates with the thin filament of sarcomeres. It controls muscle contraction and relaxation by regulating the interaction of the thick and thin filaments.

It is unknown how variants in sarcomere-related genes lead to hypertrophy of the heart muscle and problems with heart rhythm. The variants may result in production of an altered sarcomere protein or reduce the amount of the protein. An abnormality in or shortage of any one of these proteins may impair the function of the sarcomere, disrupting normal cardiac muscle contraction. Research shows that, in affected individuals, contraction and relaxation of the heart muscle are abnormal, even before hypertrophy develops. However, it is not clear how these contraction problems are related to hypertrophy or the symptoms of familial hypertrophic cardiomyopathy.

Nonfamilial hypertrophic cardiomyopathy is not caused by variants in sarcomere-related genes. The genetic cause of these cases is unknown. Researchers believe the nonfamilial form of the condition is due to a combination of genetic and environmental factors.

Familial hypertrophic cardiomyopathy is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Rarely, both copies of the gene are altered, leading to more severe signs and symptoms.

In most cases, an affected person has one parent with the condition.

Nonfamilial hypertrophic cardiomyopathy is not inherited. Its cause is complex and likely involves many genetic and environmental factors.

Familial hypertrophic cardiomyopathy (HCM) is caused by mutations in any of several known genes, and possibly other genes that have not yet been identified.Genetic testing for HCM is most informative as a "family test" rather than a test of one person. Results are most accurately interpreted after merging both genetic and medical test results from multiple family members. Ideally, the family member first having genetic testing should have a definitive diagnosis of HCM and be the most severely affected person in the family. Genetic testing of at-risk, asymptomatic relatives is possible when the responsible mutation has been identified in an affected family member. Testing should be performed in the context of formal genetic counseling.

The Genetic Testing Registry (GTR) provides information about the genetic tests for familial HCM. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

As is often the case with genetic testing in general, there are benefits and limitations of genetic testing for familial HCM. Testing may confirm the diagnosis in a person with symptoms, and may help to identify family members at risk. However, results are sometimes unclear; testing cannot detect all mutations; and results cannot be used to predict whether a person will develop symptoms, age of onset, or long-term outlook (prognosis).

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Dehydrated alcohol(Brand name: Ablysinol) - Manufactured by Belcher Pharmaceuticals, LLC
  FDA-approved indication: June 2018 approved to induce controlled cardiac septal infarction to improve exercise capacity in adults with symptomatic hypertrophic obstructive cardiomyopathy who are not candidates for surgical myectomy.

Familial hypertrophic cardiomyopathy affects an estimated 1 in 200 people worldwide. It is the most common genetic heart disease in the United States. The familial form of hypertrophic cardiomyopathy accounts for more than half of cases.

If you have a family member, especially a parent, sibling, or child, who died suddenly before age 40, let your doctor know. You might need to be screened for HCM, a genetic condition that causes the heart muscle to become thick and can lead to sudden death. While some people with HCM are very sick, many people, especially children, teens, and young adults, have no or few symptoms and may not know they have a heart problem. Sharing your family history with your doctor can help you and other relatives find HCM early, check regularly for changes to the heart, and determine the need for future treatment.

What is Hypertrophic Cardiomyopathy?

Hypertrophic cardiomyopathy is a common genetic disorder that affects about 1 in 500 people and causes the heart muscle to become thicker and stiff. This makes it harder for the heart to work properly because:

• The thickened heart muscle can obstruct blood flow out of the heart.
• The heart requires more energy and oxygen to work, especially during exercise.
• The heart can hold less blood, so the amount of blood pumped to the rest of the body with each heartbeat is decreased.

People with HCM can develop complications such as heart failure, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. HCM can lead to sudden death, especially in children, young adults, and competitive athletes, who may not be aware of their risk or have symptoms of HCM.

HCM can develop at any point in a person’s life. Most people with HCM are born with what appears to be a normal heart and develop HCM later. Those who develop HCM before age 40 often have more symptoms and complications.

Family health history, genetics, and cascade testing for HCM

HCM sometimes runs in families. In such cases, a child of an affected parent has a 50% (1 in 2) chance of having HCM.  Other family members also have an increased chance of having HCM. Importantly, the age at which other family members develop HCM can vary within families.

When collecting your family health history to assess your risk for HCM:

• Include information on family members who died suddenly, especially if they were younger than age 40.
• Include information on family members with heart failure, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, stroke, heart attack, heart transplant, or implantable cardioverter-defibrillator (ICD) (like a pacemaker).
• Update information regularly, and let your doctor know about any new diagnoses, cardiac events, or sudden deaths in your family.

HCM is caused by changes in genes that control the production of heart muscle proteins.  You only need a change in one copy of the gene to develop HCM. If someone in your family has been diagnosed with HCM, that person can have genetic testing to look for genetic changes that cause HCM. Testing in your family should start with someone who has HCM. In cases in which a young person died suddenly, genetic testing might have been done as part of the autopsy.

Once the genetic change that causes HCM is found in a person, other family members can have genetic testing for that change. If genetic testing does not find a genetic change that causes HCM in the affected family member, they should follow up with their cardiologist (heart doctor) on a regular basis. Sometimes genetic testing finds a genetic change that is not known to cause HCM at the time, but future studies show that it causes HCM. Also, further genetic testing might be recommended to include any newly identified genetic changes that cause HCM that were not included in earlier testing.

How do I know if I have HCM?

If genetic testing shows that you have the genetic change for HCM, you will need to see a cardiologist (heart doctor) to check your heart for signs of HCM. If the genetic change that causes HCM in your family is not known, parents, siblings, and children of the person with HCM will need to be checked for signs of HCM. Cardiologists can diagnose HCM using

• Echocardiogram (Echo), which is non-invasive and uses sound waves to take pictures of your heart
• Cardiac magnetic resonance imaging (MRI), which is a non-invasive way to get detailed images of your heart

Knowing the symptoms of HCM is important if you have a family health history of HCM, especially if you have the genetic change for HCM that runs in your family. Even if you don’t have a family health history of HCM, tell your doctor if you have any of the following common symptoms of HCM:

• Feeling tired or lacking energy
• Shortness of breath, especially with physical activity
• Chest pain, especially with physical activity
• Fainting or feeling dizzy or lightheaded
• Swelling in the ankles, feet, legs, or stomach

Some people with HCM do not have symptoms in the early stages but develop them over time. Thus, even if you do not currently have signs or symptoms of HCM, you might need repeated monitoring based on your age and other factors if you have a family health history of HCM, especially if you have the genetic change for HCM that runs in your family. Let your doctor know right away if you develop any of the symptoms of HCM.

What can I do if I or my child has HCM?

If you or your child has HCM, the doctor may recommend

• Regular monitoring: Adults need to see a cardiologist (heart doctor) every 3-5 years to look for changes in the heart using echocardiogram, electrocardiogram (ECG), and checking for symptoms of HCM. For children and teens, the interval is every 1-3 years.
• Medication: Currently, no medicines have been proven to prevent HCM or lower the chances of dying. However, a variety of medicines can be used to treat symptoms of HCM. New drugs are currently being tested in clinical trials that may help patients with HCM.
• Light to moderate physical activity: Light to moderate physical activity has been shown to help those with HCM. Those engaging in very high intensity activities such as competitive sports should discuss their risk with an HCM-trained specialist.
• Surgery: Your doctor might recommend surgery if you have severe HCM.
• Controlling other chronic conditions: High blood pressure, sleep apnea, and being overweight or having obesity can increase your risk of developing complications of HCM. Making lifestyle changes and taking other steps to manage these conditions are important for people with HCM.

While these steps cannot prevent HCM, they can help keep your heart as healthy as possible and decrease your likelihood of developing complications.