What is Arrhythmogenic Right Ventricular Cardiomyopathy?
Arrhythmogenic right ventricular cardiomyopathy (ARVC), also known as arrhythmogenic right ventricular dysplasia, is a genetic disorder that affects heart muscles. Over time, the condition replaces healthy heart muscle with fatty, fibrous tissue, which can disrupt normal heartbeat. This typically affects the right side of the heart, but it can also impact the left. The term “arrhythmogenic cardiomyopathy” is now being used more widely to indicate that symptoms can occur on both sides of the heart or be mostly noticeable on the left side.
ARVC is fundamentally a structural heart disease. So, it can be diagnosed by identifying functional abnormalities or evidence of fatty, fibrous heart muscle tissue. It often results in intense heartbeats that can occur with exercise, and the most dangerous complication of the disease is sudden cardiac death. It’s very important to assess individual risks for this condition because the first noticeable symptom may be cardiac arrest. Genetic testing plays a critical role in identifying such individuals at risk.
Updated diagnosis guidelines from 2020 recognize the importance of symptoms that affect both sides of the heart, or mostly the left side, which can sometimes present in unusual ways. These new guidelines also highlight the usefulness of cardiac magnetic resonance imaging—a preferred tool for diagnosing ARVC over endomyocardial biopsy, a procedure that removes a small piece of heart tissue for examination. The use of heart biopsy can miss these localized tissue changes in ARVC, leading to false negatives. Cardiac magnetic resonance imaging gives a comprehensive view of the heart structure and can detect abnormalities more accurately.
What Causes Arrhythmogenic Right Ventricular Cardiomyopathy?
ARVC is a disease caused by genetic disorders which damage the heart muscles of one or both lower chambers of the heart (ventricles). These damaged muscles are then replaced by scar-like and fatty tissue. Typically, this disease is inherited in a pattern where one copy of the altered gene in each cell is enough to cause the condition. However, not everyone who inherits the gene will show symptoms, and when symptoms do appear, they can vary from person to person in the same family.
According to research, about two-thirds of people with ARVC test positive for a genetic disorder. The condition is mainly caused by changes in eight different genes. Out of these, five are ‘desmosomal’ genes (genes that help cells stick together), and the other three are ‘non-desmosomal’ genes. Studies show that 50-60% of people with ARVC have changes in the genes that make desmosomal proteins. The most frequent gene change occurs in the PKP2 gene, representing 20-46% of cases, with DSP and DSG2 genes each showing changes in about 10% of cases. People with changes affecting both ventricles of the heart are more likely to have changes in non-desmosomal genes.
A rare condition known as Naxos disease, caused by changes in the JUP gene, is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have alterations. This affects a protein necessary for cells to stick together properly. When these proteins are disrupted, it leads to excessively thick skin on the palms of the hands and soles of the feet, and excessively curly hair. Naxos disease affects nine out of ten people who inherit the genetic changes. Carvajal syndrome is a similarly inherited heart condition, much like Naxos disease, but it usually starts to show symptoms earlier in childhood.
Risk Factors and Frequency for Arrhythmogenic Right Ventricular Cardiomyopathy
ARVC, or arrhythmogenic right ventricular cardiomyopathy, is a heart condition that is not very common, but when it does occur, it can be severe. It’s seen more frequently in places like Italy and Germany, with estimates suggesting it affects about 1 out of every 2,000 to 5,000 people. Men are somewhat more likely to have ARVC and it tends to be more severe in them, possibly due to differences in hormones or physical activity levels. Although it’s not a common condition, it’s particularly concerning because it can cause sudden heart-related death in young people.
- ARVC is a heart condition that affects about 1 in 2,000 to 5,000 people in countries like Italy and Germany.
- It tends to be a bit more common and severe in men, possibly due to differences in hormones or the intensity of physical activity.
- Despite being relatively rare, ARVC can lead to sudden death from heart issues in young individuals.
Signs and Symptoms of Arrhythmogenic Right Ventricular Cardiomyopathy
ARVC, typically diagnosed in individuals between the ages of 20 and 40, is known for symptoms like heart palpitations, feeling faint or passing out (syncope) during physical activities. Other common symptoms are:
- Heart palpitations (Experienced by 30%-60% of patients)
- Feeling lightheaded (20%)
- Passing out (10%-30%)
However, it’s important to note that not all patients will experience preceding symptoms. About 60% of the ones who have a sudden heart attack may not have experienced any of the typical symptoms. In fact, sudden cardiac death can be the first indicator of ARVC in some individuals, with up to 20% of the diagnosed patients’ first symptom being cardiac arrest.
The development of ARVC generally follows three stages:
- Concealed stage
- Clinically overt stage
- Right, left, or both-sided heart failure (occurs in about 50% of patients)
During the concealed stage, ARVC may not show any significant heart structure abnormalities, and patients may not have any symptoms. However, cardiac arrest can still occur at this stage.
In the next stage, the “clinically overt stage”, abnormal changes in the heart’s architecture become detectable, and heart rhythm problems (arrhythmias) become evident. These arrhythmias can range from premature heartbeats originating from the ventricles (the lower chambers of the heart), non-permanent or long-lasting ventricular tachycardia (rapid heart rate), to potentially fatal ventricular fibrillation. Arrhythmias developing in the atrium (upper chambers), such as atrial fibrillation, are also more common in ARVC patients. It’s worth noting that up to 60% of patients may initially show up with a non-life-threatening form of ventricular tachycardia.
Over time, some patients may progress to the stage of heart failure, affecting either the right, left, or both sides of the heart. About half of ARVC patients may experience at least one symptom of heart failure, commonly feeling short of breath during physical exertion. Heart failure serves as the most common reason for heart transplantation in relation to ARVC and is strongly linked to sudden cardiac death.
The symptoms of ARVC can sometimes mimic those of other cardiac conditions. Patients may present chest pain and elevated cardiac enzymes (proteins involved in heart function) that are suggestive of heart muscle inflammation (myocarditis), despite no evidence of any arterial blockage (coronary artery disease). This presentation is particularly common in specific genetic variants of ARVC and especially in children with this condition. Therefore, unexplained pediatric myocarditis, especially with a family history, should prompt testing for ARVC.
In some types of ARVC, skin and hair changes are also notable. For example, patients with Naxos Disease and other variants of ARVC can present with thick, wooly hair and hair loss (alopecia). They may also have certain skin conditions like eczema, fragile skin, sores around the mouth or buttocks, and blister-like lesions similar to a skin disorder called pemphigus. Dental abnormalities and changes in the nail texture (nail dystrophy) have also been reported. Infants carrying certain genetic mutations related to ARVC have shown lethal skin conditions (neonatal lethal epidermolysis).
Testing for Arrhythmogenic Right Ventricular Cardiomyopathy
Various tests are needed to evaluate a disease called ARVC. One standard test is the electrocardiogram (EKG), which usually shows irregularities in ARVC patients, such as abnormal T-waves and potentially incomplete right bundle-branch block, which pertains to a specific type of heart rhythm disorder.
More serious symptoms like ventricular tachycardia, which is a rapid heart rate from improper electrical activity, can arise and turn into a dangerous heart rhythm disorder called ventricular fibrillation. These conditions can be triggered or worsened by physical activities that increase heart rate. Ventricular ectopy, a condition involving extra heartbeats initiating from the ventricles, can occur from different sections of the right ventricle.
An epsilon wave, a specific type of wave found in the EKG, can be identified in half of ARVC patients. These waves originate from abnormal electrical impulses and usually appear at the end of one EKG segment and the beginning of another. They point to a delayed activation of the right ventricle.
A test called Holter monitoring might be recommended for a period of 24 hours to detect any presence of abnormal rhythms, especially in those who experience symptoms. Intermittent ventricular arrhythmias, which refer to irregular heartbeats initiated in the lower chambers of the heart, may be identified during this testing.
Another commonly used tool to detect ARVC is echocardiography, a test that uses sound waves to create images of the heart. This test may reveal an enlarged or abnormally functioning right ventricle. Other irregular changes may also be observed. Sometimes, the left ventricle and the septum of the heart can also show abnormalities. Patients with ARVC for a longer duration may develop severe right or both ventricles failure. Regular follow-ups with echocardiography are done depending on the patient’s condition.
Cardiac magnetic resonance (CMR) is another tool that is extremely effective for observing the right ventricle. CMR can identify abnormalities like fatty infiltration and can also measure right ventricle volume, function, and irregularities in the movement of the heart wall. Computed tomography scan, also known as a CT scan, can be used if CMR is not suitable, but it provides less clear images.
In rare cases, electrophysiological studies are performed. These studies help differentiate ARVC from other heart conditions.
Endomyocardial biopsy, a test in which a small sample of the right ventricle is removed for examination, can provide specific evidence for ARVC but can possibly miss the diagnosis as the sample might not be taken from the infected part of the heart. This biopsy is not essential if other criteria convincingly suggest ARVC.
Cardiac catheterization, a procedure to examine how well the heart is working by inserting a thin, hollow tube called a catheter into the heart through a blood vessel, is rarely performed. This test is usually done when differentiating ARVC from a birth defect of the heart or in preparation for a biopsy.
Treatment Options for Arrhythmogenic Right Ventricular Cardiomyopathy
The purpose of treating ARVC (arrhythmogenic right ventricular cardiomyopathy), a heart disease, is to decrease the risk of sudden heart failure, slow down disease progression, and improve patient quality of life by reducing heart failure symptoms and arrhythmia. Treatment can involve clinical management, medicine, a procedure called catheter ablation, installing a cardiac defibrillator, or in some cases, a heart transplant.
Firstly, clinical management involves limiting physical activity. Exercise could trigger arrhythmia and speed up how fast the disease progresses. This is advised to everyone diagnosed with ARVC, even if they aren’t showing symptoms, to reduce the risk of sudden heart failure and to delay the disease’s symptoms.
Medicinal treatment aims to control arrhythmia, prevent blood clot formation, and manage heart failure. Beta-blockers, particularly long-lasting ones like metoprolol, are recommended since they can prevent arrhythmias and lessen the strain on the heart wall. If ventricular arrhythmias continue despite using sotalol, Amiodarone or combined therapy with flecainide may be considered. Standard medications for right or left heart failure can be used, and patients with atrial fibrillation or blood-clot complications can use anticoagulants.
Radiofrequency catheter ablation is an option for patients with uncontrolled ventricular tachycardia. It is recommended for those with repeated episodes of tachycardia or those with repeated defibrillator discharges, despite medication. However, the tachycardia may return in 50% to 75% of patients over three years due to disease progression.
A cardiac defibrillator is highly effective in preventing sudden heart failure. It is particularly suggested for patients with a history of cardiac arrest due to tachycardia or fibrillation, severe ventricular impairment, or suspected arrhythmia-induced episodes of non-sustained ventricular tachycardia and syncope, among others. However, it does have risks such as infections, so it’s typically not given as a preventive step to healthy gene carriers or those without symptoms or risk factors.
Last but not least, heart transplantations can be considered for patients with uncontrolled arrhythmias or for those whose ventricular failure cannot be controlled with medication. The survival rates after a heart transplantation are significant, with 81% surviving 5 years post-transplant and 77% surviving 10 years post-transplant.
What else can Arrhythmogenic Right Ventricular Cardiomyopathy be?
ARVC is an uncommon heart condition that doctors can confuse with other heart illnesses because they have similar symptoms. Three of these illnesses include right ventricular outflow tract tachycardia, Brugada syndrome, and cardiac sarcoidosis.
Right ventricular outflow tract tachycardia may appear similar to ARVC. However, there are distinguishing factors. For example, it isn’t inherited, doesn’t involve a gene mutation, and doesn’t cause diverse, persistent rapid heartbeats like ARVC does. Also, the heart waves in ARVC are usually inverted, but this isn’t usual in right ventricular outflow tract tachycardia. Imaging tests can also differentiate between the two because the latter doesn’t show any irregular fatty infiltrations in the heart muscle, like ARVC does.
Brugada syndrome and ARVC share some similarities; they’re both inherited and associated with the SCN5A gene. A heart wave test, or electrocardiogram, can display a variety of wave patterns in Brugada syndrome, unlike ARVC. Furthermore, Brugada syndrome doesn’t cause any noticeable changes to the heart’s structure and is more common in Southeast Asia, while ARVC is more prevalent in European countries like Greece and Italy.
Cardiac sarcoidosis may be difficult to distinguish from ARVC in imaging tests. Some indicators favor cardiac sarcoidosis diagnosis: lymph nodes in the chest area, older age when symptoms first appear, non-familial disease patterns, certain gadolinium-enhanced images of a heart wall, higher glucose activity in the heart’s muscle observed in a PET scan, and irregular heart rhythm patterns. In some cases, a heart tissue biopsy may be required to confirm the diagnosis.
Some congenital heart diseases like Ebstein anomaly, certain types of heart disease like Uhl anomaly, and blood flow abnormalities in the heart can mimic ARVC symptoms. However, imaging tests can typically differentiate these conditions.
Left-sided dominant ARVC shares similarities with various heart diseases like muscular dystrophies, myocarditis, cardiac sarcoidosis, congenital heart defects, and Chagas heart disease. However, a distinguishing feature is that the irregular distribution of muscle and fatty tissue in ARVC starts from the outer layer of the heart and spreads to the inner layer over time.
What to expect with Arrhythmogenic Right Ventricular Cardiomyopathy
The annual death rate for patients with ARVC, a heart muscle disorder, can be anywhere from 0.08% to 3.6%. However, for those who receive treatment, this typically falls below 1%. The health outlook for patients with ARVC is largely based on how severe their irregular heartbeats (arrhythmias) are and how inefficient their heart chambers (ventricles) are working. An important predictor of recurring dangerous arrhythmias is a previous incident of fainting (syncope) happened due to a fast heart rate (sustained ventricular tachycardia) or cardiac arrest caused by a very rapid and erratic heartbeat (ventricular fibrillation).
There are other risk factors that could lead to arrhythmic events, such as persistent or temporary episodes of ventricular tachycardia and impaired heart function.
Prime risk factors for sudden cardiac death or life-threatening arrhythmia include:
* A past incident of cardiac arrest due to ventricular arrhythmia
* A history of unexplained fainting
* Non-persistent fast heartbeat identified during an exercise stress test or ongoing monitoring.
* Significantly reduced pumping ability of the right, left, or both heart chambers.
Smaller risk factors embrace having more than 1000 premature heartbeats in a day, evidence of certain abnormalities on an electrocardiogram (a test that checks heart’s electrical activity), known genetic abnormalities, younger age at diagnosis, and being male.
Possible Complications When Diagnosed with Arrhythmogenic Right Ventricular Cardiomyopathy
Complications can arise when ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) isn’t treated, is being diagnosed, or even during its treatment. Without treatment, the disease can progress leading to other issues like an abnormally fast heart rate, heart failure, sudden death, clot formation that can affect other organs, and general organ failure. Notably, the type of ARVC can influence what complications they might face. For instance, those with the PKP2 type often have serious right heart issues, while individuals with the DSG2 type are more likely to develop heart failure-related problems and may require a heart transplant.
Treatment for ARVC isn’t without its risks. Having an intracardiac defibrillator can result in a small annual risk of unnecessary shocks and infections or device malfunctions. Medications that regulate heart rhythm can also cause an abnormally long heart beat rhythm, and clot-preventing medications can result in minor or severe bleeding.
Even diagnostic processes carry their own risks. An invasive test called endomyocardial biopsy may cause damage to the heart or its internal structures. Due to these risks, it is used only in specific circumstances, such as cases where there’s no family history of ARVC, and genetic tests are negative. The test can help confirm ARVC or similar heart diseases by looking for abnormal changes in the heart tissue. It also helps rule out other conditions that may mimic ARVC, like cardiac sarcoidosis.
Preventing Arrhythmogenic Right Ventricular Cardiomyopathy
Doctors should correctly identify people who might have ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy), a heart muscle disorder, as this condition can potentially lead to a sudden heart failure. The main aim is to spot those who are at a higher risk of sudden heart failure or long-lasting fast heartbeats. Various factors like age, gender, electrical characteristics of the heart, and results of heart images are taken into account.
For people who show no symptoms but are definitively diagnosed with ARVC, it’s recommended to limit physical activities and get re-checked every 1 to 2 years. Patients should be aware of their risks and expected outcomes, and actively participate in their care through joint decision-making. Relatives should also be appropriately checked for ARVC.
It’s very important that patients understand their treatment options because of the risk of sudden heart failure, and potential side effects of drugs to correct heart rhythms and ICDs (Implantable Cardioverter Defibrillators), such as unexpected shocks.
