Cardiovascular
Heart Disease – Cardiovascular Testing Services
There are various types of inherited heart disease, including arrhythmias, congenital heart disease, cardiomyopathy, and high blood cholesterol. Coronary artery disease leading to heart attack, stroke, and heart failure can run in families, indicating inherited genetic risk factors.
What type of patients should be tested?
- Any patient that is exhibiting cardiac symptoms or with a family history of cardiac disease.
- Unexplained cardiac arrest or sudden deaths in the family that might have been caused by an undiagnosed heart disease
- Unexplained fainting, or fainting with exercise or emotional stress
- Unexplained seizures, or seizures with normal neurological evaluation
- ICD/pacemaker at under 50 years of age
- Irregular heartbeat
- Heart failure at less than 60 years of age
- Enlarged heart
- Early heart attack, coronary artery disease or stroke (men under 55, women under 65)
- Enlarged aorta or aortic aneurysm in the chest at less than 55 years of age
- Sudden infant death syndrome (SIDS) in the family
- Untreated very high cholesterol level
- Heart defect present since birth
About Heart Disease
Genetics can influence the risk for heart disease in many ways. Genes control every aspect of the cardiovascular system, from the strength of the blood vessels to the way cells in the heart communicate. A genetic mutation in a single gene can affect the likelihood of developing heart disease. For example, a genetic variation can change the way a protein works so that the body processes cholesterol differently, increasing the likelihood of blocked arteries. Genetic variations are passed from parents to children in the DNA of the eggs and sperm. The parents’ genetic code is then copied into every cell of a child’s body during development.
When a family member is diagnosed with heart disease or a heart disorder, other family members are encouraged to undergo screening for risk factors and early stage disease that may not yet produce symptoms.
Inherited conditions that lead to arrhythmias and sudden cardiac death are particularly well understood. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy (ARVC) both can cause deadly arrhythmias. There are several inherited disorders that can cause arrhythmias and sudden cardiac death. Some of these are very rare. They include:
- Arrthymogenic Right Ventricular Dysplasia
- Brugada Syndrome
- Cardiac Amyloidosis
- Familial Dilated Cardiomyopathy
- Familial Valvular Heart Disease
- Hypertrophic Cardiomyopathy
- Long QT syndrome
- Loeys-Dietz Syndrome
- Marfan Syndrome
- Noncompaction Cardiomyopathy
- Restrictive Cardiomyopathy
Identifying these conditions early on can lead to better care and improved health over time. Improved health can come from earlier screenings for certain diseases, changes in lifestyle related to diet and exercise and possibly eliminating risks like smoking.
ARVD/C
The goal of genetic testing is to identify the genetic change causing ARVD or Arrhythmogenic Right Ventricular Dysplasia (also known as Arrhythmogenic Right Ventricular Cardiomyopathy – ARVC) in a family. This can then be traced through the family to identify who else may have inherited that genetic change.
ARVD is a rare familial disorder that can cause ventricular tachycardia and sudden cardiac death in young, and often times, healthy individuals. The clinical hallmark of the disease is a ventricular arrhythmia, arising predominantly from the right ventricle. Fibrofatty replacement of the right ventricular myocardium is the hallmark of the disease. ARVD is more common in athletes, due to the way the disease presents it is seen as a delayed onset of the disease.
Patients generally begin to show signs of ARVD sometime after puberty but before the age of 50. The diagnosis of ARVD is challenging and requires the performing of several cardiac tests such as:
- Electrocardiogram
- Signal Averaged Electrocardiogram
- 24-hour Holter Monitor
- Exercise Stress Test
- Echocardiogram
- Cardiac Magnetic Resonance Imaging (MRI)
- Cardiac Computed Tomography (CT)
- Genetic Testing
- Electrophysiology Study
- Right Ventriculogram (RV angiogram)
- Cardiac Biopsy
Once diagnosed, it is recommended for most patients that an implantable defibrillator be placed in order to prevent the possibility of sudden death. Antiarrhythmic drug therapy and catheter ablation also play important roles in treatment. It’s important to note that with advances in the field of medicine, the role of genetic testing is increasing. It is helping more than ever in evaluating and diagnosing patients who are suspected to have ARVD and, thereby, guiding therapy options.
Brugada Syndrome
Brugada syndrome is an inherited condition with a specific abnormal heartbeat, called a Brugada sign which causes the lower ventricles of the heart to beat so fast that the blood cannot circulate throughout the body well. This irregular heart rhythm can cause fainting or sudden cardiac arrest oftentimes in healthy individuals. The Brugada syndrome is also known as SUDS (Sudden Unexplained Death Syndrome) and SADS (Sudden Adult Death Syndrome) and is most common in people of Asian ancestry and more often in men.
Approximately 20% of the cases to date of Brugada syndrome have been shown to be associated with genetic mutations. The cause of death in Brugada syndrome is ventricular fibrillation. The episodes of syncope and sudden death are caused by fast polymorphic ventricular tachycardias or ventricular fibrillation. These arrhythmias appear with no warning. While there is no exact treatment modality that reliably and totally prevents ventricular fibrillation from occurring, treatment lies in the termination of this lethal arrhythmia before it causes death.
Cardiac Amyloidosis
Cardiac amyloidosis is a manifestation of one of several systemic diseases known as the amyloidoses. This uncommon disease is often under-diagnosed, as there are several types of amyloids and each has its own unique features and methods of treatment. Therefore, it is often hard to identify which can lead to errors in the management of patient care.
Cardiac involvement in amyloidosis (which can range from no signs to severe signs) is derived from a light-chain precursor (AL amyloidosis). Secondary amyloidosis almost never affects the heart in any clinically significant manner. The specific composition of the fibrils differs in the different types of amyloid. Both on the basis of common usage and for the sake of simplicity, “cardiac amyloidosis” is used here to describe the involvement of the heart by amyloid deposition, whether as part of systemic amyloidosis (as is most commonly the case) or as a localized phenomenon.
Cardiac Myxoma
A Cardiac Myxoma (also known as an Atrial Myxoma) is a noncancerous tumor found in the upper left or right side of the heart. The tumor most often grows on the wall (atrial septum) that separates the two sides of the heart and is benign. It is known as a primary heart tumor meaning it starts in the heart, which is normally not the case with most heart tumors. It occurs more often in women and is passed down through the genetic line in families (roughly 1 out of 10 are passed from parent to child). The tumor is most often found in the left atrium of the heart (~75%) and begins in the wall that divides the heart’s upper two chambers. The rest are found in the right atrium and those found here are sometimes linked to Tricuspid Stenosis or Atrial Fibrillation.
Symptoms may occur at any time, but most often they go along with a change in body position. It also depends on which side the myxoma is located on: Left atrial myxomas result in symptoms produced early on and often mimic mitral stenosis while right atrial myxomas do not produce any symptoms until they’ve grown at least 5″ in width.
The most common symptoms are as follows:
- Breathing difficulty when lying flat
- Breathing difficulty when asleep
- Chest pain or tightness
- Dizziness
- Fainting
- The sensation of feeling your heartbeat (palpitations)
- Shortness of breath with activity
Other symptoms may include:
- The blueness of the skin, especially on the fingers (Raynaud’s phenomenon)
- Cough
- The curvature of nails accompanied by soft tissue swelling (clubbing) of the fingers
- Fever
- Fingers that change color upon pressure or with cold or stress
- General discomfort (malaise)
- Joint pain
- Swelling in any part of the body
- Weight loss without trying
A myxoma is not cancerous, but complications are common and if left untreated could lead to embolism (tumor cells breaking off and traveling in the bloodstream). This could lead to a blockage of blood flow or cause the tumor to grow in another part of the body. Pieces of the tumor can move to the brain, eye, or limbs. In addition, if the tumor grows inside the heart and is not removed surgically, it could block blood flow and could result in sudden death. Other possible complications that could result from cardiac myxomas are:
- Arrhythmias
- Pulmonary edema
- Peripheral emboli
- Spread (metastasis) of the tumor
- Blockage of the mitral heart valve
Dilated Cardiomyopathy
Dilated cardiomyopathy also is known as Familial Dilated Cardiomyopathy or DCM is a genetic condition passed down from parent to child in which the heart becomes weakened and enlarged and cannot pump blood efficiently. Decreased heart function can affect the lungs, liver, and other body systems. DCM is one of the cardiomyopathies, a group of diseases that affect primarily the myocardium. During DCM a portion of the myocardium is dilated, often without any obvious cause. The left or right ventricular systolic pump function of the heart is impaired leading to progressive cardiac enlargement and hypertrophy, a process called remodeling. Dilated cardiomyopathy is also the most common form of non-ischemic cardiomyopathy. It occurs in both adults and children and more frequently in men than in women. In addition, DCM is more common in African Americans than in Caucasians, though it can occur in any patient population.
In adults, it is most common between the ages of 20 – 60 years and causes congestive heart failure (CHF) in ~1 in 3 cases. Although in many cases no cause (etiology) is apparent, DCM is probably the result of damage to the myocardium produced by a variety of toxic, metabolic, or infectious agents. It may be due to fibrous change of the myocardium from a previous myocardial infarction (heart attack), or it may be the late sequelae of acute viral myocarditis.
Other causes include:
- Chagas disease is the most common infectious cause of DCM.
- Pregnancy can also lead to DCM, but occurs late in the gestation period or several weeks to months postpartum & is reversible in half of the cases.
- Alcohol abuse
- Thyroid disease, stimulant use, and chronic uncontrolled tachycardia.
- Autoimmune mechanisms
About 25–35% of patients have familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins, while some affect other proteins involved in contraction. The disease is genetically heterogeneous, but the most common form of its transmission is an autosomal dominant pattern. Rarer forms of the transmission of this disease do exist, such as autosomal recessive, X-linked, and mitochondrial inheritance.
DCM may not cause symptoms that have a significant, if not immediate, effect on an individual’s quality of life. However, this does not mean that significant symptoms do not occur.
Some such symptoms are:
- Breathlessness
- Syncope
- Angina
Valvular Heart Disease
Valvular heart disease is any disease process involving one or more of the four valves of the heart (the aortic endometrial valves on the left and the pulmonary and tricuspid valves on the right). Collectively, the valves are part of the dense connective tissue makeup of the heart known as the cardiac skeleton. Valve problems may be congenital or acquired. Despite a dramatic decline in the incidence of rheumatic heart disease in industrialized countries, VHD remains highly prevalent and the disease encompasses heart valve defects (i.e. bicuspid aortic valve, myxomatous mitral valve prolapse) that are inherited from family members. The early signs of VHD usually do not begin to surface until adulthood and both men and women are equally susceptible to this disease.
Recent advances in our understanding of the genetic basis of familial VHD have been made through the unraveling of gene network and molecular mechanisms regulating normal valve development.
Types of VHD:
- Aortic insufficiency / Regurgitation
- Mitral Valve Stenosis
- Aortic Valve Stenosis
- Mitral Insufficiency / Regurgitation
- Tricuspid Insufficiency / Regurgitation
- Mitral Valve Prolapse
- Rheumatic Fever
- Endocarditis
Symptoms Include:
- Heart Failure (Mitral valve stenosis, Aortic stenosis, Aortic insufficiency, Mitral insufficiency)
- Palpitations (Mitral valve stenosis, Aortic insufficiency)
- Chest Pain (Mitral valve stenosis)
- Hemoptysis (Mitral valve stenosis)
- Syncope (Aortic stenosis)
- Thromboembolism (Mitral valve stenosis)
- Ascites (Mitral valve stenosis)
- Edema (Mitral valve stenosis)
- Angina Pectoris (Aortic stenosis, Aortic insufficiency)
- Pulmonary Edema (Mitral insufficiency)
- Right-sided heart failure (Tricuspid insufficiency)
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a disease that causes the wall of the heart muscle to thicken impacting the efficiency of the heart muscle and causing obstruction of blood flow. HCM is also an inherited disease and is associated with abnormal heart rhythms, which can sometimes be life-threatening.
People with HCM can have the following symptoms:
- Shortness of breath
- Chest pain or discomfort
- Fainting
- Palpitations or the sensation of feeling the heartbeat
- Dizziness
A minority of people with HCM will suffer from the most serious complications (i.e. sudden death, heart failure and/or stroke). It is important to note that HCM has a wide range of severity and some people may not experience any symptoms for quite a while. They could have normal heart evaluations well into their adulthood without showing any signs, while others may begin to show signs/ symptoms starting at a very young age. It is difficult to predict whether a patient will have a mild or severe form of the disease. Although the disease is extremely rare in the athletic population, it remains the #1 cause of sudden death in athletes during strenuous exercise.
Diagnosis of HCM requires thorough cardiology, a physical exam (thus listening to the heart and lungs for any abnormalities), a genetics evaluation, and a complete medical history (including family medical history). Additional tests typically include echocardiography and electrocardiogram (ECG). If tests are not conclusive, your doctor will require further tests that include a cardiac MRI, a stress test, monitoring for abnormal heart rhythms and cardiac catheterization.
Genetic Link
Being a genetic cardiac disease, if a patient is diagnosed with HCM, then their immediate family members need to undergo genetic tests to see if they also carry it. Family members can be tested for that same genetic mutation and should be followed up every few years by a cardiologist. By finding which member has the gene mutation, it can arm the carrier with knowledge on how to preserve their health while avoiding strenuous exercise. They can seek regular care with a cardiologist, who may prescribe specific medications or arrange for a pacemaker or defibrillator to be implanted.
Long QT Syndrome
Long QT syndrome (LQTS) is an abnormality in the heart’s electrical system that causes very fast and potentially dangerous heart rhythms, leading to a sudden loss of consciousness and in some cases — sudden cardiac death. The term “Long QT” refers to the abnormal pattern on an electrocardiogram (ECG). The “QT” interval is the ECG measure of the period when the lower chambers of your heart (the ventricles) are triggered to contract and then prepare to contract again. Long QT occurs when the contraction interval is longer than normal.
Although the exact frequency of LQTS is unknown, it may cause 2,000 to 3,000 sudden deaths in children and young adults each year in the U.S. The most common symptom is a sudden loss of consciousness or fainting, called Syncope. The condition may also cause seizures and in some instances, cardiac arrest and sudden death. These symptoms do not always occur and thus, the severity of the condition varies greatly. Some people never experience syncope and others may have frequent episodes. It is important to note that symptoms usually occur without warning and are caused by a very fast heart rhythm called torsade de pointes. Syncope may occur during or just after physical exertion, emotional excitement or sudden auditory arousal, such as from an alarm clock.
LQTS is usually diagnosed with an electrocardiogram (ECG). However, the ECG isn’t a perfect test for the condition because some people with the disorder will have normal tests, or tests might be normal on some days and abnormal on other days.
LQTS is usually inherited, which means it may affect multiple family members. Each child, irrespective of gender, has a 50% chance of inheriting the genetic mutation that causes the condition of his/her parent. Once a family member is identified with the condition, it is very important to test all other family members. All close relatives should see a cardiologist and have an ECG as well.
Genetic testing can also help diagnose LQTS. Once genetic testing has identified the genetic mutation causing the condition in a family, other family members can be tested for that same genetic mutation to see if they also inherited it. Such testing can also determine which sub-type of LQTS your family has, although it cannot find the cause of the mutation. Knowing which sub-type of LQTS a patient has can help determine which is the best mode of treatment for him/ her.
Loeys-Dietz Syndrome
Loeys-Dietz syndrome (LDS) is a genetic disorder that affects the connective tissue in the body. Individuals with LDS exhibit a variety of medical features in the cardiovascular, musculoskeletal, skin and gastrointestinal systems. Although it is an inherited disease, it cannot be tested the same way as other genetic cardiovascular diseases because no two individuals will show the same identical medical characteristics.
The main clinical characteristics include:
- Widely spaced eyes
- Cleft palate or bifid uvula
- Aortic and arterial aneurysms/dissections with the corkscrew structure of the arteries
Other findings can include:
- Scoliosis or Kyphosis
- Indented or protruding chest wall
- Contractures of fingers and toes
- Long fingers and lax joints
- Club foot
- Premature fusion of the skull bones
- Joint hypermobility
- Congenital heart problems including patent ductus arteriosus
- Atrial septal defect
- The translucency of the skin with a velvety texture
- Abnormal junction of the brain and medulla
- Bicuspid aortic valves
Marfan Syndrome
Marfan syndrome is a rare, inherited disorder of connective tissue and growth. The disease affects several parts of the body and is highly variable, which means that different people with the condition will have different parts of their body affected to a greater or lesser degree. The features of the disease result from changes in the body’s connective tissue and in the control of body growth. Connective tissue holds our bodies together and is found throughout the body, which is why Marfan Syndrome can affect many different parts of the body.
The most common and serious feature of Marfan syndrome is dilation or widening of the aorta, which is the main blood vessel carrying blood from the heart to the entire body. The dilation can progress until the wall of the aorta tears, a condition called aortic dissection. This is the most serious or life-threatening feature of Marfan syndrome. However, aortic dissection can be avoided by taking appropriate medicine and also with preventive surgery to replace a dilated aorta before it tears.
Since Marfan syndrome is partly caused by changes in growth regulation, people with the disorder can often have some of the following traits:
- They are taller than people in their family who do not have Marfan syndrome
- They may have long, thin fingers and long arms and legs
- They may have a dislocation of the lens in the eye that also causes nearsightedness or myopia that can progress quickly
- They may have a detached retina, early glaucoma or early cataracts
There is not one simple test to make a diagnosis for Marfan syndrome, so when a patient is being checked for the possibility of the condition there are a few features that need to be looked for. These features consist of observing four skeletal signs with one or more signs in another body system, such as ocular and cardiovascular in one individual before further testing can be considered. The most common and serious feature of Marfan syndrome is the dilation or widening of the aorta, which is the main blood vessel that carries blood out of the heart to the rest of the body.
Genetic testing can help with the diagnosis because it can look to see if the FBN1 gene has a mutation. Since this gene is hereditary, if the FBN1 mutation is found in a patient then the rest of the family should also be tested.
Noncompaction Cardiomyopathy
Noncompaction cardiomyopathy is a heart muscle condition that occurs in the left ventricle when the muscular wall of the main pumping chamber of the heart becomes spongy and “non-compacted”. This type of cardiomyopathy is not fully understood and is a topic of ongoing research. Moreover, it is difficult to predict the prognosis of people affected by this condition. Non-compaction cardiomyopathy is thought to result from a halt in the normal development of a fully thick compacted surrounding wall for the heart muscle. This abnormal development reduces the mass of the heart muscle and blood circulation.
Symptoms caused by noncompaction cardiomyopathy are not specific and are mainly determined by how much heart function is affected. Individuals who have the described structural features, but the normal performance of the heart, maybe entirely free of symptoms. Typical symptoms that may appear are usually:
- S.O.B. (shortness of breath)
- Fatigue
- Swelling of the lower extremities
- limited physical capacity and exercise intolerance
This condition is also thought to be associated with an increased risk of blood clots in the meshwork of prominent heart muscle bands. In other words, the blood flow in this region is relatively slow compared to other parts of the heart. Another risk possibly associated with this condition is a fast cardiac rhythm, which may result in a drop in blood pressure, loss of consciousness and, if not treated, death in rare cases.
Restrictive Cardiomyopathy
Restrictive cardiomyopathy refers to a set of changes in how the heart muscle functions, and is one of the causes for cardiac amyloidosis. These changes cause the heart to fill poorly (more common) or squeeze poorly (less common). Sometimes, both problems are present. In a case of restrictive cardiomyopathy, the heart muscle is normal size or slightly enlarged. Most of the time it also pumps normally. However, it does not relax normally during the time between heartbeats when the blood returns from the body (diastole). When the disease progresses, the heart may not pump blood strongly. The abnormal heart function can affect the lungs, liver, and other body systems. Restrictive cardiomyopathy may affect either or both of the lower heart chambers (ventricles). It is very often linked to a disease of the heart muscle. Restrictive cardiomyopathy is a rare condition. The most common causes, in addition to amyloidosis, are scarring of the heart from an unknown cause (idiopathic myocardial fibrosis). It also can occur after a heart transplant.
Causes:
- Carcinoid heart disease
- Diseases of the heart lining (endocardium), such as endomyocardial fibrosis and Loeffler’s syndrome (rare)
- Iron overload (hemochromatosis)
- Sarcoidosis
- Scarring after radiation or chemotherapy
- Scleroderma
- Tumors of the heart
Symptoms:
- Cough
- Breathing problems that occur at night
- Fatigue and inability to exercise
- Loss of appetite
- Swelling of the abdomen
- Swelling of the feet and ankles
- Uneven or rapid pulse
- Chest pain
- Lack of focus
- Low urine output
- Need to urinate at night (in adults)
- Testing :
- Cardiac catheterization and coronary angiography
- Chest CT scan
- Chest x-ray
- ECG (electrocardiogram)
- Echocardiogram and Doppler study
- MRI of the heart
- Nuclear heart scan (MUGA, RNV)
- Serum iron studies
- Serum or urine protein tests
Symptoms caused by noncompaction cardiomyopathy are not specific and are mainly determined by how much heart function is affected. Individuals who have the described structural features, but the normal performance of the heart, maybe entirely free of symptoms. Typical symptoms that may appear are usually:
- S.O.B. (shortness of breath)
- Fatigue
- Swelling of the lower extremities
- limited physical capacity and exercise intolerance
This condition is also thought to be associated with an increased risk of blood clots in the meshwork of prominent heart muscle bands. In other words, the blood flow in this region is relatively slow compared to other parts of the heart. Another risk possibly associated with this condition is a fast cardiac rhythm, which may result in a drop in blood pressure, loss of consciousness and, if not treated, death in rare cases.
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