Arrhythmogenic Cardiomyopathy

What Is Arrhythmogenic Right Ventricular Cardiomyopathy & What Causes It?

Despite the commonly used name, arrhythmogenic cardiomyopathy is not restricted to the right ventricle. This is just the variety that was first identified. Research has found that there are several types of ACM, including variants that predominantly affect the right ventricle (ARVC; also called arrhythmogenic right ventricular dysplasia [ARVD]), the left ventricle (left-dominant arrhythmogenic cardiomyopathy [LDAC]) or both (biventricular arrhythmogenic cardiomyopathy).

Regardless of the type of ACM you have, the same issue occurs, wherein your heart muscle is replaced with scar tissue (fibrosis) and (often) fat due to an inherited genetic condition. The fibrosis and fat affect the transmission of electrical signals through your heart, affecting how it beats. As a result, you may experience arrhythmias or irregular heartbeats. These arrhythmias in some patients can cause the individual to lose consciousness or even die suddenly. Similarly, because the heart cannot beat as effectively or normally, it is not as competent at pumping blood around your body. In extreme circumstances, this can then lead to heart failure.

It is important to know, though, that ACM can vary between individuals. While some may experience progressive heart issues, others may find the disease remains stable. Others again may have very minor changes that can only be detected by a skilled cardiologist who is intimately familiarly with the disease.

As a genetic heart condition, ACM is usually inherited and cannot be acquired. In order to develop ACM, you need to inherit it from a parent or have the relevant gene spontaneously mutate at conception. While ACM is autosomal dominant (this means that only one half of the pair of genes needs to be affected for you to inherit the condition), who is affected and how severely varies greatly. 

While research is ongoing into which genes and mutations are responsible for the condition, many have been identified and are well understood. For instance, research has identified that changes to the junction plakoglobin (JUP) or desmocollin (DSC2) genes often mean the patient has ARVC rather than LDAC. In contrast, mutations in the desmoplakin (DSP) gene are more likely to cause LDAC or biventricular ACM. Knowing which genes and mutations can cause ACM allows doctors to use genetic testing to confirm an ACM diagnosis.

Do You Have Arrhythmogenic Right Ventricular Cardiomyopathy Symptoms?

While it’s estimated that ACM affects between 1 in 1,000 to 5,000 people, it’s also acknowledged that the condition can often be misdiagnosed or missed, so the real number is unknown. Therefore, understanding what symptoms of ACM can look like is important to achieve an accurate and quick diagnosis.

Depending on how the condition has progressed, the symptoms of arrhythmogenic right ventricular cardiomyopathy can include:

• Thickening of the skin on the palms of your hands or soles of your feet (palmoplantar keratoderma)
• Tightly curled and/or brittle hair
• Occasional or rapid palpitations (arrhythmias)
• Feeling lightheaded or dizzy, or fainting (syncope)
• Chest discomfort
• Intermittent shortness of breath

Some symptoms are evidence of structural changes to your heart (like arrhythmias or syncope), while others indicate that the proteins in your body are being affected (like changes to your skin and hair). Generally, though, it is the dangerous ventricular arrhythmias with related symptoms (like fainting, palpitations or cardiac arrest) that lead people to being diagnosed with ACM.

Your ACM symptoms may not become apparent until you are in your mid-20s to mid-30s. However, like other inherited heart conditions, for instance Long QT syndrome, arrhythmogenic cardiomyopathy symptoms may not be present or obvious even at that age. There are instances where a person may have ACM but have barely noticeable or ‘concealed’ structural changes to the heart, even when carefully examined. They may also have little to no symptoms, including having no clear arrhythmias. This does not mean that the heart is not affected. Nor is the person not at risk of complications. Therefore, it is worthwhile to look at a family health history, including careful evaluation of instances of sudden cardiac death, particularly of young and active relatives, to see if ACM is a possibility. Specialised genetic testing is often vital in helping make the picture clearer and achieve an earlier diagnosis.

Additionally, similar to heart conditions like hypertrophic cardiomyopathy, sudden death of an otherwise healthy, and even young, person may be the first sign of the condition in the family. Reviewing your family health history if you have any of these symptoms, however mild, can help you get an earlier diagnosis. With this earlier diagnosis, you can then begin treatment immediately and prevent further damage to your heart.

How Do I Get an Arrhythmogenic Right Ventricular Cardiomyopathy Diagnosis?

Currently, there are a complex set of diagnostic criteria called the Task Force Criteria that doctors use to make a diagnosis of ACM. A service with expertise in ACM will look to gather information from a number of clinical sources to determine if an ACM diagnosis is accurate. This will help avoid a misdiagnosis, as there are many non-genetic conditions that can mimic ACM. For example, inflammation of the heart muscle (myocarditis) caused by a viral infection, or severe coronary artery disease (where the arteries are narrowed due to fat accumulation, leading to the heart muscle being starved of blood. This is particularly severe in conditions like familial hypercholesterolaemia).

As part of a comprehensive evaluation for the possibility of ACM, your physician will recommend you have an ECG (electrocardiogram), echocardiogram (echo), 24-hour heart rhythm monitor (Holter monitor) and a cardiac MRI (magnetic resonance imaging) scan to look for evidence of changes to your heart’s structure, including the presence of fibrofatty tissue.

If the results from these tests indicate that ACM is a possible or likely diagnosis, genetic testing for arrhythmogenic right ventricular cardiomyopathy is strongly recommended. Whilst the combination of results from the above tests and relevant family health history are important, in some cases specialised genetic testing with expert interpretation is the only way to be certain that ACM is the diagnosis. Then, once the diagnosis of ACM is made, genetic testing can be offered to other members of your family to identify individuals who are at risk of sudden death and need immediate attention. 

For accurate genetic testing, it is best to work with a service that truly understands the nuances of cardiac genetics, including just how variable the conditions can be between people and how serious they are. This ensures that they are able to arrange the appropriate genetic tests and interpret them accurately to aid in treatment and management. This specialisation is something that Progenics is built on.

How Genetic Testing Can Help

Genetic testing provides a level of detail that is difficult to rival through other clinical evaluations. Firstly, it confirms a suspected diagnosis, including which mutations are involved. This then makes it easier to create a more effective treatment and management plan for an improved prognosis and quality of life. 

Secondly, your positive results indicate to physicians caring for other family members that these family members need to be tested too as soon as possible. Because ACM can seriously affect your heart health, an early diagnosis is one of the most important treatment steps. Through genetic testing, you can help affected family members get diagnosed sooner.

Are There Signs of Arrhythmogenic Right Ventricular Cardiomyopathy in Your Family Tree?

While genetic testing has come a long way in a very short time, any genetic service will tell you that we have just begun to scratch the surface of genes, their mutations and the conditions they cause. As a result, it is possible to have ACM but a genetic test to come back as negative or inconclusive. Therefore, your family health history is just as important a tool for achieving a correct and timely diagnosis.