Can't find an answer to your ARVD question? Please contact the ARVD coordinator at Johns Hopkins. We want to hear from you!

What is ARVD?
ARVD stands for Arrhythmogenic Right Ventricular Dysplasia. Arrhythmogenic means causing an arrhythmia. The right ventricle is the chamber of the heart that is affected and dysplasia means there is an abnormality of the structure. ARVD is a specific type of cardiomyopathy (a disorder of the cardiac muscle).

Simply put, ARVD is a genetic, progressive heart condition in which the muscle of the right ventricle is replaced by fat and fibrosis, which causes abnormal heart rhythms. ARVD is estimated to affect one in 5,000 people. The disease can affect both men and women. Although it is a relatively uncommon cause of sudden cardiac death, it accounts for up to one fifth of sudden cardiac death in people under 35 years of age.

[Return to Top]

What is an arrhythmia?
An arrhythmia is an abnormal heart rhythm. At rest, the heart normally beats with a regular rhythm at 60 to 100 beats per minute. Tachycardia is when the heart beats too fast and bradycardia is when the heart beats too slow. The arrhythmia can be described further by indicating what part of the heart is starting the abnormal rhythm. If the arrhythmia is coming from the ventricle, it is called a ventricular arrhythmia. There are several types of ventricular arrhythmias. PVCs are premature ventricular contractions, which are the most common type of ventricular arrhythmias. Many people have isolated PVCs and have healthy hearts. PVCs can alternate with the normal rhythm in a regular pattern. If the ratio is one normal beat to one PVC, the rhythm is called bigeminy. If the ratio is two normal beats to one PVC, it is called trigeminy. Ventricular tachycardia (VT) is a run of more than 3 consecutive PVCs. An arrhythmia can be short lasting, called unsustained, or long lasting, called sustained. A sustained rate of over 120 beats per minute will usually require medical treatment. Very fast ventricular arrhythmias can be life-threatening.

[Return to Top]

What are symptoms of ARVD?
The symptoms of ARVD are usually a result of an arrhythmia. Many people do not know they have an arrhythmia. There are many different symptoms of an arrhythmia and healthy people without ARVD can have these symptoms. When you feel your heart speed up or slow down or feel it pounding, it is called palpitation. Palpitations are a normal response to fright or exertion but can, in other circumstances, be abnormal. If the change in rhythm makes it difficult for the heart to pump blood, other symptoms can occur such as lightheadedness and fainting (also called syncope). Arrhythmias can also impair the flow of blood to the heart muscle and cause chest pain, which is also called angina. An arrhythmia can also cause sudden death if the heart cannot pump enough blood to its own muscle and to the lungs and body. Fortunately, sudden death is not a common complication, but the risk must be considered when deciding on the treatment.

Sometimes people with ARVD develop symptoms of heart failure. Heart failure means that the heart muscle is not pumping blood through the body effectively. Symptoms include swelling of the legs, feet, and abdomen; feelings of shortness of breath while lying down and while exercising, and feelings of extreme fatigue.

In addition to these common symptoms of arrhythmias and heart failure other symptoms individuals with ARVD have reported include nausea, dizziness, heart fluttering, heart racing, etc.

[Return to Top]

How is ARVD diagnosed?
It is often difficult to diagnose ARVD and there is no single test which can alone definitively make or exclude the diagnosis. However, the results of a careful medical history, physical exam by a nurse or doctor and a number of cardiac tests can be used to make a diagnosis. The cardiac tests are an electrocardiogram (ECG), a signal averaged ECG (SAECG), an exercise stress test, an echocardiogram, cardiac MRI and a 24-hour Holter monitor. It is extremely important that the cardiac MRI be performed at in institution familiar in doing cardiac MRI's to evaluate for ARVD, as these studies are difficult to interpret accurately. In addition to these standard tests, an electrophysiology study (EP study), right ventriculogram, and biopsy may be recommended to completely evaluate for ARVD. Other tests that provide information about the heart structure and function include a CT scan and MUGA scan. An autopsy can show ARVD if the heart is carefully examined.

There is a set of criteria that are based on the finding of certain major and minor findings on cardiac tests and on the family history. A list of the criteria can be found elsewhere on this website.

[Return to Top]

How is ARVD treated?
Treatment focuses on controlling the arrhythmias and in managing any signs or symptoms of heart failure. Most people with ARVD take medications called antiarrhythmic agents which can help lessen the frequency and severity of arrhythmias. A common treatment for ARVD is the implantation of an implantable cardioverter defibrillator (ICD). This device monitors the heart's rhythm and delivers an electrical shock to the heart to return it to the normal rhythm if necessary. Sometimes an electrophysiology study (EP study) can determine which areas of the heart are causing the abnormal rhythm, and these areas can be eliminated (ablated). However, because ARVD is a progressive disease, the arrhythmias are not permanently cured by this procedure.

Individuals with signs or symptoms of heart failure are treated with medications. These medications include ACE inhibitors which make it easier for the heart to pump blood and diuretics which reduce symptoms of heart failure. Although there is not yet a proven benefit to ACE inhibitors in ARVD patients without heart failure symptoms, many doctors are now treating patients prophylactically to help delay the progression of ARVD.

The most extreme treatment of ARVD is to have a heart transplant. This is rarely necessary. It is used only when the heart is very weak or when arrhythmias cannot be controlled no other treatment is successful.

[Return to Top]

Once ARVD is diagnosed, how is it managed?
Once ARVD has been diagnosed, the majority of patients undergo implantation of an implantable cardioverter defibrillator (ICD). In general, this will require that you see your doctor for an ICD check-up every 3-6 months. In addition, the status and progression of your ARVD should be monitored with yearly echocardiograms and electrocardiograms. Some institutions may also be able to perform a cardiac MRI depending on the type of ICD that you have. Your doctor may also request additional testing, such as a CT scan or stress test every couple of years. A close working relationship with your doctor is necessary to monitor the effectiveness of your medications in controlling your arrhythmias.

[Return to Top]

What is the prognosis of ARVD?
In our experience, the majority of patients who stop exercising early on in the course of their ARVD do quite well. Once the arrhythmias are controlled with medication and an ICD is in place, very few individuals die from ARVD. However, now that the ICD is the recommended treatment offering protection from sudden cardiac death, individuals with ARVD are living longer. This means there may be more individuals with heart failure requiring a heart transplant in the future.

[Return to Top]

What causes ARVD?
There is a lot of evidence that ARVD is a genetic, heritable condition where an affected person has a chance of passing on a specific gene change to his or her children. There is also some evidence that ARVD could result from an infection of the heart muscle. One or both theories could be correct. For instance, an infection in someone with a certain genetic make-up could cause ARVD.

In general, someone who inherits a gene change or mutation for ARVD has inherited a genetic predisposition to developing ARVD. A single gene change is usually not sufficient for the development of ARVD. We think that for most individuals, additional factors such as other genes, athletic lifestyle, exposure to certain viruses, etc. are needed for an individual to actually develop signs and symptoms of ARVD. This is an area of very active research and we have a lot to learn about all the factors that can cause ARVD.

There are rarer forms of ARVD that have been shown to be passed on in a family in an autosomal recessive pattern. This means that both parents of someone affected with ARVD carry a gene change for ARVD but they do not have ARVD themselves. However, each of their children has a 25% chance of inheriting both copies of the gene change which results in the development of ARVD. This type of pattern is seen in Naxos disease, a variant of ARVD predominantly seen in Greece.

[Return to Top]

How is ARVD inherited?
To help explain the inheritance of ARVD, let us back up and explain some concepts of biology. Our bodies are made up of cells and in each cell in the nucleus, is DNA. The DNA is a string of messages that we call genes. Genes are like sentences in that certain letters are put together to make a code that are the instructions for telling our bodies how to look and function. If a letter or letters from a sentence or missing or added in the wrong place, the genetic sentence will not make sense and can result in genetic disorders like ARVD. These gene changes can be passed on from one generation to the next. In general you have two copies of every gene, one from your mother and one from you father.

ARVD can be inherited in 2 different ways: autosomal dominant inheritance with reduced penetrance and autosomal recessive inheritance. In autosomal dominant inheritance, a person with a gene change predisposing them to ARVD has a 50% chance of passing on that same predisposition to their child. We know that not everyone who inherits a gene change associated with ARVD will develop ARVD. This is called “reduced penetrance”. Among people in a family who get ARVD there is variation in the severity of the disease and the age that ARVD starts. We are working hard to figure out what genetic and other factors predict which people with a genetic change go on to develop ARVD.

In autosomal recessive inheritance, an individual has to have two copies of a gene associated with ARVD to get the disease. A person has a 25% chance of inheriting both copies of the gene changes responsible for ARVD (one from dad and one from mom). Each parent “carries” a gene change but does not have ARVD. This type of pattern is seen in Naxos disease, a variant of ARVD predominantly seen in Greece . Autosomal dominant appears to be the most common pattern of inheritance.

[Return to Top]

What genes are associated with ARVD?
Known ARVD variants with inheritance pattern (AD = autosomal dominant, AR = autosomal recessive), chromosome location, and name of gene if known .

Seven genes (plakoglobin, plakophilin-2, desmoplakin, ryanodine receptor-2, transforming growth factor beta-3, desmoglein-2, and desmocollin-2) and their exact gene changes have been identified and published to date.

[Return to Top]

Is there a genetic test for ARVD?

Clinical genetic testing for plakophilin-2 (PKP2), desmoplakin (DSP), desmoglein-2 (DSG2), desmocollin-2 (DSC2), plakoglobin (JUP), transmembrane protein 43 (TMEM43), and ryanodine receptor 2 (RYR2) is now available in the United States through a number of different clinical laboratories listed below. The labs vary in price, number of genes screened, and technology used.

Harvard Laboratory for Molecular Medicine http://www.hpcgg.org/
GeneDx http://www.genedx.com/
PGxHealth http://www.pgxhealth.com/index.cfm
Correlagen Diagnostics http://www.correlagen.com/index.jsp
The Hospital of Sick Kids in Toronto, Canada http://www.sickkids.ca/molecular/

If you are interested in finding out more about genetic testing for ARVD, please contact one of our genetic counselors at 410-502-7161 for more information. We are happy to work with you, your physicians, and your insurance company in understanding the risks, benefits, and limitations of genetic testing in your specific situation. There are many research laboratories that offer testing on a research basis, however, many of these labs are unable to provide results or require clinical confirmation of a research result. There are some institutions outside of the United States (Canada, France, Netherlands, and Germany) that offer clinical testing for plakophilin-2, ryanodine receptor, desmoplakin, desmoglein-2, and desmocollin-2. We strongly recommend that you meet with a genetic counselor (www.nsgc.org) beforehand to discuss the benefits, risks, and limitations of genetic testing. Interpretation of genetic test results for ARVD can be quite complex.

[Return to Top]

If someone in my family has ARVD, should everyone be screened?
There is a lot of evidence that ARVD is genetic and as a result, there are some recommendations for other family members. After the diagnosis is made in one person, all of his or her first-degree relatives should be screened. First-degree relatives are siblings, parents and children of someone diagnosed with ARVD. If another person in the family is then found to be affected, then all of their first-degree relatives of that person need to be screened. This is called stepwise screening. To further explain this, take an example of Joe who is diagnosed with ARVD. Joe's first-degree relatives (his siblings, parents and children) are all screened in step 1. Joe's father, Ed is also affected. Now in step 2, Ed's first-degree relatives need to be screened. This process is repeated until all at-risk relatives have been screened. If a more distant relative has symptoms of an arrhythmia, we would recommend that person be screened as well.

While ARVD is most commonly diagnosed in adults in their 20s and 30s, both children and older people have been diagnosed. Children who have an affected parent should see a pediatric cardiologist to discuss appropriate cardiac testing. Similarly, older relatives, though they may not appear to have any symptoms, should still be tested because they may have mild symptoms of ARVD.

[Return to Top]

If I have ARVD, what tests do my first degree relatives need to have done?
Unfortunately, no single cardiac test can diagnose ARVD. First degree relatives need to have all 6 of the tests listed below in order to determine if they are affected or unaffected. These tests are necessary in order to determine if someone meets the diagnostic criteria.

The tests are:

Standard 12 lead ECG
Signal averaged ECG with 40mHz filter
Holter monitor for 24 hours
Echocardiogram
Exercise stress test
Cardiac MRI

It may be necessary to have more cardiac testing if some of the above tests are abnormal. The additional testing may be needed to clarify indeterminate results of the previous tests.

[Return to Top]

How often should family members be screened for ARVD?
First-degree family members of an individual diagnosed with ARVD should be evaluated every 2-5 years with an ECG, signal averaged ECG, exercise stress test, 24-hour Holter monitor, echocardiogram, and cardiac MRI. The recommended time period for repeat screening will vary among family members depending on results of previous testing, reported symptoms, and family history.

[Return to Top]

Can an infant or young child be diagnosed with ARVD?
Yes, but it is rare. Young children rarely have symptoms and are rarely affected. Several of these tests are not routinely performed on children or may require sedation in order to be performed. Thus, cardiac testing young children should be discussed with your cardiologist and pediatrician who may refer your child to a pediatric cardiologist. Testing recommendations will vary depending on the child 's symptoms and family history. Teenagers can have symptoms and should have an evaluation in order to establish a baseline. At this time no formal guidelines have been established or published. Click here for screening recommendations from Johns Hopkins.

[Return to Top]

What should I know about participating in genetic research studies?
When you agree to participate in any study, you should take the time to read the consent form carefully. Ash questions if you don 't understand something. Many genetic research studies do not release results, mainly because the laboratory that the genetic research is being performed in is not a CLIA certified lab. CLIA stands for Clinical Laboratory Improvement Amendment . The role of the CLIA program is to ensure quality laboratory testing. Research labs are not required to adhere to any special regulations. In the majority of cases when you donate a blood sample for research, a unique number, not your name, is written on the sample tube. There is always the chance for a sample mix-up, mislabeling, or inactive reagents resulting in an inaccurate results.

[Return to Top]

What should I know about genetic research being performed at Johns Hopkins?
If you meet the diagnostic criteria for ARVD, you may have provided a blood sample as part of the Clinical and Genetic Investigations of ARVD study at Johns Hopkins. We have been screening blood samples from individuals meeting the diagnostic criteria for gene changes thought to be associated with ARVD. Although the Johns Hopkins Institutional Review Board does not permit us to release research results, we will notify you if a result becomes available and will assist you in obtaining clinical confirmation testing through a CLIA certified laboratory. There is a fee associated with this confirmation testing. This confirmation testing is important as samples may become mixed up or mislabeled since they are labeled with a research number only and not your name. Genetic results should not be used to determine management until they are confirmed in a CLIA certified laboratory.

[Return to Top]

If I have ARVD, should I get an implantable cardioverter defibrillator (ICD)?
Not every patient with ARVD needs to have an ICD. Each person's medical case is different, so it is best to discuss this with your doctor. ICDs are not a cure although they have been shown to effectively treat episodes of ventricular tachycardia and ventricular fibrillation in ARVD patients. However, there have not been any studies directly comparing how ARVD patients with and without ICD's do.. There are some studies that show heart attack patients with non-sustained ventricular tachycardia do better with ICD than with medication. However, these study patients have different heart abnormalities than ARVD patients.

[Return to Top]

If I have ARVD, can I exercise?
The exact relationship between ARVD and exercise is not clear. For many patients with ARVD, exercise can be an immediate cause of arrhythmia. There seems to be an increased incidence of ARVD in young very athletic people, particularly men. There are also numerous reports of sudden cardiac death from ARVD that occur during physical exertion. In addition, the gene changes recently found in many people with ARVD are in genes that hold heart muscle cells together. We think that exercise, therefore, puts an extra strain on these already weak heart muscle connections. Therefore, it's possible that an athletic lifestyle for someone who has inherited a genetic predisposition for ARVD may be sufficient for that individual to develop ARVD. Therefore, we recommend that patients with ARVD should not do vigorous exercise. It is best to discuss with your doctor about what types of exercise are appropriate for you.

[Return to Top]

Is pregnancy safe for someone with ARVD?
Although there is very limited information on pregnancy in individuals with ARVD, W w omen with ARVD have had uncomplicated pregnancies, even when on medications or with an ICD. There are some medications that can harm the baby as it develops, and your doctor may recommend that you switch medications on a temporary basis. at least temporarily. Pregnancy does put extra strain on the heart, and thus, if you are planning a pregnancy, or become pregnant you should see your cardiologist and obstetrician as early as possible. You should discuss with your doctor about medication options during delivery, delivery options, and monitoring of your heart during labor.

[Return to Top]

Do ARVD patients have to avoid any medications or substances that exacerbate VT?
Patients who are prone to arrhythmias, caused by ARVD or other conditions, are generally advised to avoid stimulants of all kinds. Stimulants include nicotine and caffeine as well as pharmacological stimulants such as Sudafed (pseudoephedrine), which is commonly used in cold and flu medications. Patients prone to arrhythmias are advised to limit their intake of alcohol, a depressant, which is also proven to cause arrhythmias.

If you take medications to suppress your arrhythmias, such as Atenolol or another beta blocker, and your arrhythmia is under control, then moderate exposure to stimulants should not be problematic. This means go ahead and take the cold medicine for a week or two, or have an occasional bar of chocolate, just don't take either in huge amounts for a long time! Arrhythmias can be provoked for many different reasons when you are ill, including fever, electrolyte imbalance and decreased absorption of the anti-arrhythmia medication. People who are predisposed to arrhythmias may have more arrhythmias when they are ill, but it is difficult, if not impossible, to be sure of the exact cause. Thus, our advice is to use cold medications only as needed, but read the labels and ask your pharmacist about the stimulant content, so you know what you are taking.

Patients with ARVD can get arrhythmias without an increase in stimulants or exposure to alcohol. These arrhythmias can happen at any time, because the heart has an abnormal ability to conduct electrical impulses. Although it is human nature to try to find a cause and effect relationship, there will not be an identifiable cause for all arrhythmias. Understanding this is true and that one cannot control for all the variables that cause or effect an arrhythmia, may help patients in coping with the unpredictable nature of their symptoms.

[Return to Top]