Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy is a genetic cardiomyopathy thought to affect 1 in 5,000 people, where the heart muscle (myocardium) is replaced by both scar (fibrosis) and fat. This can affect predominantly the right ventricle, the left ventricle, or both ventricles. The replacement of normal heart muscle by fibrosis has two major effects. First, it affects normal transmission of the electrical signals through the heart, leading to heart rhythm disorders (arrhythmias), which can be potentially life-threatening. Second, it can cause a decrease in cardiac function and increase the risk of heart failure.

There are three types of arrhythmogenic cardiomyopathy:

• Arrhythmogenic right ventricular cardiomyopathy (ARVC), the most well-known type of the condition, which affects mainly the right ventricle. This is sometimes referred to as arrhythmogenic right ventricular dysplasia (ARVD).
• Left-dominant arrhythmogenic cardiomyopathy, which mainly affect only the left ventricle
• Biventricular arrhythmogenic cardiomyopathy, which affects both ventricles

These can include:

• Occasional or rapid palpitations which may be associated with lightheadedness and dizziness
• Syncope (sudden loss of consciousness)
• Cardiac arrest
• Heart failure

Inflammation is an important aspect of the condition, and some patients have myocarditis (inflammation of the heart muscle) associated with chest pain. This often occurs more than once with no other identified cause (such as a viral infection).

Some patients may also have flaky, itchy, or cracked skin on the palms of their hands and soles of their feet (palmoplantar keratoderma); tightly curled, brittle hair; or dental changes. This is because the proteins associated with the condition are not only found in the heart, but also in the skin, hair, and teeth.

The usual age of onset is in mid-20s to mid-30s, but the condition is increasingly recognized in children. Why this occurs in some patients in childhood in unclear.

Arrhythmogenic cardiomyopathy frequently runs in families, although the degree to which different individuals within any one family are affected is highly variable.

For decades, arrhythmogenic cardiomyopathy was thought to affect just the right ventricle, leading to the term arrhythmogenic right ventricular cardiomyopathy. In 2008, several patients and families with left ventricular-dominant disease were reported. Since then, researchers have found that a protein called plakophilin 2 is associated more commonly with AVRC and desmoplakin is associated with the left-dominant form of the disease.

Arrhythmogenic cardiomyopathy is diagnosed using both cardiac and genetic testing. A detailed family history can identify other family members who already are or may be affected. Cardiac testing includes an electrocardiogram (ECG), cardiac imaging using echocardiograms or cardiac magnetic resonance imaging (MRI), and a 24-hour ECG recording (Holter monitor). If a specific genetic change (mutation) has been identified in the family, this can also be used to identify other family members at risk of developing the condition.

Arrhythmogenic cardiomyopathy may be misdiagnosed, especially in children. It can often be mistaken for myocarditis caused by a viral infection, ventricular arrhythmia, or a benign arrhythmia.

Children with no symptoms might not need medication or other treatment right away. Instead, the cardiologist will monitor your child to gauge the progression of the disease.

A child with more serious symptoms may need additional tests to give the health care team more detailed information about how the cardiomyopathy is affecting the heart.

Treatments for arrhythmogenic cardiomyopathy may include:

• Medications to help regulate heart rhythm, such as beta-blockers implantable loop recorders to monitor the heart rate and rhythm over a prolonged period of time, especially in patients who may be having symptoms
• An implantable cardioverter-defibrillator (ICD) to monitor heartbeat and administer an electrical pulse to regulate the heart rhythm if the child has a life-threatening arrhythmia
• Treatment of heart failure symptoms, which in the most severe cases may require a heart transplant

At Boston Children’s Hospital, patients with arrhythmogenic cardiomyopathy are cared for primarily by the Inherited Cardiac Arrhythmia Program with involvement of other teams within the Center for Cardiovascular Genetics as appropriate.

Boston Children’s is one of the most experienced programs for arrhythmogenic cardiomyopathy in North America. Our team is working very closely with colleagues at Harvard Medical School and other centers around North America and Europe to better understand the condition in younger patients.