What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloidosis-Associated Heart Disease
• Heart Amyloidosis
• Stiff Heart Syndrome

What is Cardiac Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins)
• These protein aggregates are abnormally-formed and arranged into fibrils (slender fibers). An amyloid build-up can occur locally in only one organ, or may occur throughout the body. When the abnormal amyloid proteins get deposited in the heart tissue, it results in Cardiac Amyloidosis. The condition typically affects older adults
• There are 5 major types of amyloidosis, all of which can lead to Cardiac Amyloidosis:
  • AL amyloidosis that occurs when bone marrow produces too much amyloid protein, creating light (L) chains
  • AA amyloidosis, when amyloid proteins build up secondary to a chronic disease
  • Hereditary amyloidosis: It is an inherited form of the disease; the amyloid build-up primarily affects the kidneys and nerves
  • Wild-type ATTR amyloidosis: This form leads to amyloid protein deposits in elderly adults, particularly in the heart and tendons
  • Dialysis-related amyloidosis: This occurs in individuals who have undergone dialysis for a long time. The amyloid protein tends to get deposited in the tendons and joints
• Among the above, the two types that are most likely to affect and damage the heart are AL amyloidosis and transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a presentation of wild-type ATTR amyloidosis that can cause heart failure from long-term stiffness in the heart muscles
• Cardiac Amyloidosis may present with symptoms of irregular heartbeats, difficulty breathing, and chest pain. The condition can lead to restrictive cardiomyopathy and can fatal, if left untreated

Who gets Cardiac Amyloidosis? (Age and Sex Distribution)

• Cardiac Amyloidosis can affect individuals of any age, although older individuals are affected the most. This condition is rare in individuals under 40 years of age
• Cardiac Amyloidosis occurs more frequently in men than women
• Individuals of all races and ethnic groups may be affected
• The heart may be involved in almost all subtypes of amyloidosis

What are the Risk Factors for Cardiac Amyloidosis? (Predisposing Factors)

The following are some known risk factors for developing Cardiac Amyloidosis:

• Advancing age
• Male gender
• A family history of amyloidosis
• Any condition that affects the antibody-producing cells in the body, including benign monoclonal gammopathy, malignant lymphoma, and multiple myeloma
• Long-term kidney dialysis
• Chronic inflammatory conditions such as
  • Arthritis, including rheumatoid arthritis, juvenile inflammatory arthritis, psoriatic arthritis and ankylosing spondylitis
  • Inflammatory bowel disease (IBD) such as ulcerative colitis
• Chronic infections, including
  • Tuberculosis
  • Leprosy
  • Bronchiectasis
  • Osteomyelitis
  • Skin infections (especially in drug abusers, who use needles to inject themselves)
  • Chronic infection in skin with burns
  • Chronic kidney infections (pyelonephritis)
  • Whipple’s disease
• Poorly-controlled diabetes
• Infectious diseases such as HIV/AIDS
• Cystic fibrosis; individuals with this condition are prone to repeat infections
• Certain cancers such as Hodgkin’s lymphoma and renal cell carcinoma
• Family history of certain hereditary disorders that may include:
  • Familial Mediterranean fever (FMF)
  • Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)
  • Hyperimmunoglobulin D syndrome and periodic fever syndrome (HIDS)
  • Cryopyrin-associated periodic syndrome (CAPS)
  • Majeed syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cardiac Amyloidosis? (Etiology)

• Cardiac Amyloidosis is usually caused by any of the following subtypes of amyloidosis such as:
  • AA amyloidosis
  • AL amyloidosis - light chain amyloidosis is reported to be a common cause of Cardiac Amyloidosis
  • Hereditary amyloidosis
  • Wild-type ATTR amyloidosis - this can result in transthyretin amyloid cardiomyopathy (ATTR-CM), another leading factor that can cause Cardiac Amyloidosis
  • Dialysis-related amyloidosis
• In the above subtypes, the abnormal protein misfolding results in amyloid protein formation. The amyloid protein fibrils circulate in the bloodstream and get deposited in the heart tissue, causing symptoms of Cardiac Amyloidosis
• With time, extensive amyloid protein deposits make the heart muscles lose its elasticity, resulting in severe complications including heart failure. When the elasticity is lost, the heart is known as a “stiff heart”

What are the Signs and Symptoms of Cardiac Amyloidosis?

The signs and symptoms of Cardiac Amyloidosis may vary among the affected individuals in severity and may include:

• Anemia
• Fatigue
• Decreased urine output; increased urge to urinate at night time
• Shortness of breath with physical exertion or while lying down
• Irregular heartbeats
• Chest pain
• Enlargement of heart; fluid build-up around the heart
• Excess cholesterol in blood
• Unintended weight loss
• Edema, or swelling, in abdomen, hands, feet, legs and face

Since Cardiac Amyloidosis is present as a manifestation of systemic amyloidosis, symptoms pertaining to other affected organs may also be present. The following are some general signs and symptoms that may overlap with symptoms of Cardiac Amyloidosis:

• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Joint pain
• Skin rashes, which may be purple or red spots
• Rash around eyes
• Eyes that appear puffy
• Tingling sensation; numbness
• Clay-colored stools
• Carpal tunnel syndrome (resulting in weak grip)
• Bleeding disorders; problems with proper clotting of blood

How is Cardiac Amyloidosis Diagnosed?

The diagnosis of Cardiac Amyloidosis may include general tests to ascertain the subtype of amyloidosis (and its underlying cause), as well as specific tests to assess damage to the structure and function of heart.

The following methods may be used to diagnose Cardiac Amyloidosis:

• A thorough physical examination
• Evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood test to assess:
  • Complete blood count (CBC)
  • Heart disease markers 
  • Level of iron in blood
• Chest X-ray to check for heart size, contour, or fluid build-up in lungs
• Electrocardiogram (EKG), to check the electrical activity of the heart
• Echocardiography (or echo): The use of sound waves to create images of the heart, as it functions. This helps to check the size, shape, and pumping function of the heart 
• Other imaging studies of the heart using computed topography (CT) scan and magnetic resonance imaging (MRI) scan techniques
• Nuclear imaging of the heart with “multigated acquisition” scan (MUGA scan), to determine the heart’s pumping function (specifically, the functioning of the ventricles)
• Cardiac catheterization: It is a technique that is used to check for pressure and blood flow in the heart chambers. It is often coupled with coronary angiography, in which a harmless dye is injected into the coronary arteries and with the help of an X-ray, blood flow through the heart and blood vessels can be observed
• Additional imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-ray of the affected region
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Myocardial biopsy: A very tiny piece of the heart is removed and the cells are investigated for changes that may suggest damage to heart muscle. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In Cardiac Amyloidosis,
  • Immunohistochemical analysis of tissue samples using anti-AA serum, to identify the type of amyloidosis an individual has
  • Amyloid deposit from affected tissue is detected using a staining procedure. When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)
  • The biopsy can also provide information on myocardial infection, if any present
• Bone marrow aspiration for checking the type of abnormal immunoglobulin light chains
• Molecular genetic testing to check for mutation(s) in the TTR gene, which is the most common gene affected in hereditary amyloidosis
• Molecular testing to check the type of proteins in amyloid deposits (AL or AA chains) through mass spectrophotometry

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cardiac Amyloidosis?

The potential complications of Cardiac Amyloidosis include:

• Dizziness and risk of fall, if one stands up too quickly from a seated position
• Episodes of fainting
• Increase in sensitivity to a type of heart medication called digoxin
• Ventricular arrhythmias: Abnormal heart rhythms, which can be triggered by physical exertion
• Sick-sinus syndrome: A condition in which the individual has a very slow or very fast heart rate, alternating slow and fast heart rate, or stopped heart
• Sudden cardiac arrest
• Embolism: Development of blood clots in the heart which may get into the bloodstream and obstruct blood supply to many vital organs
• Stroke

How is Cardiac Amyloidosis Treated?

Currently, there are no treatment options to cure Cardiac Amyloidosis. The treatment methods are geared towards:

• Easing the symptoms of the condition
• Slowing its progression

The following treatment measures may be used to address the symptoms specific to abnormal heart function:

• Lifestyle changes:
  • Adhering to a healthy diet that includes fresh fruits, vegetables, whole grains, fish and dairy products
  • Engaging in routine physical activity
  • Smoking cessation
  • Losing excess weight
  • Avoiding alcohol and illicit drugs
  • Getting enough sleep
  • Avoiding or reducing of stress
• Prescription medications such as:
  • Beta blockers and calcium channel blockers are generally the first choice of medicines to treat cardiomyopathies, in order to regulate heartbeat
  • Digoxin, to improve heart function and increase activity level
  • Diuretics, to remove excess fluid and sodium from the body
  • Electrolytes to aid in the proper functioning of muscles and nerve tissues
  • Anti-coagulants or blood thinners, which prevent blood clot formation
  • Anti-inflammatory drugs, to reduce inflammation 
• Non-surgical procedures such as alcohol septal ablation
• Surgical procedures, through the use of surgically-implanted devices:
  • Implantable cardioverter defibrillator (ICD): It is a small device implanted in the chest or abdomen and connected to the heart via wires. The device helps control life-threatening arrhythmias that can lead to sudden cardiac arrest. The procedure is typically recommended for younger individuals
  • Pacemakers, generally recommended for older adults
  • Left ventricular assist devices (LVADs) or heart pumps

• In severe cases, a heart transplantation may be necessary

It must be noted that amyloidosis is usually systemic, affecting multiple organs at the same time. Therefore, additional treatments pertaining to the subtype of amyloidosis and its underlying cause are often necessary.

How can Cardiac Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Cardiac Amyloidosis
• If there is a family history of Amyloidosis, then genetic counseling will help assess risks, before planning for a child
• Seeking prompt medical attention for pre-existing conditions that can lead to amyloidosis, which consequently causes Cardiac Amyloidosis is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Cardiac Amyloidosis? (Outcomes/Resolutions)

• The prognosis of Cardiac Amyloidosis is determined by a number of factors, such as the extent of disease, overall health of the affected individual, and his/her response to treatment
• With timely and appropriate treatment, it is possible to delay progression of the condition and have a good quality of life for several years
• However, a delayed diagnosis and/or treatment can lead to several complications of the heart and other organs, which can be fatal

Additional and relevant Useful Information for Cardiac Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum