Amyloidosis

Misfolded proteins mimicking muscle

What is Amyloidosis?

Amyloidosis is a disease caused by abnormal proteins in the body. The proteins gather in different organs, so they don't work well. This buildup is called "amyloid plaques."

What causes different types of Amyloidosis?

There are several types of Amyloidosis with different causes. AA type starts with a reaction to an illness and usually affects the kidneys, not the heart. It is much less common than the other types. We will focus on other types that do affect the heart. AL type is caused by a bone marrow disorder. Hereditary type is caused by a gene mutation and is passed down in families. Wild-type has no clear origin.

How is Amyloidosis like HCM? 

Some forms of Amyloidosis affect the heart and can look like HCM. On imaging tests, ATTR-type and AL-type hearts look alike. Other tests will be needed to tell one type from another and to tell them from HCM.

How is Amyloidosis diagnosed?

If a doctor suspects amyloidosis, they will order tests to confirm this and figure out what type it is. Lab tests using blood and urine are often done first. These may be followed by a sample of tissue such as fat (called a biopsy). Bone marrow may also be tested. Sometimes, another area of the body may be biopsied, such as the liver, kidney, heart, or stomach. Imaging such as echocardiogram will be used if amyloidosis is affecting the heart.

Blood and Urine tests for Amyloidosis

Blood and urine tests can help confirm the diagnosis of amyloidosis. They can also help to find organs involved and how they’re affected. Cardiac tests for troponin, BNP, and NT-proBNP show whether the heart is under stress. Other tests look for stress in organs such as the kidneys.

Genetic Testing/Family screening

Genetic testing will be used to see if amyloidosis is a hereditary type. If it is, the family can be tested for the detected genetic variant. This information can also be used to tailor treatment for the variant.

EKG/ECG

Like HCM, abnormal EKGs are common in those with cardiac amyloidosis. The EKG may indicate a possible past myocardial infarction (heart attack) when there hasn't been one. Some may have conduction abnormalities or arrhythmias. Regular EKGs and holter or ambulatory monitors can help screen for any problems.

Echocardiogram

An echocardiogram can show the effects of amyloid deposits on the heart. Often, the entire heart is enlarged. Both atria (upper chambers) may be thick or dilated. Both ventricles (lower chambers) are often thick. The heart valve leaflets may be thick.

MRI/CMR

Cardiac MRI (CMR) can help to show where in the heart amyloid has gathered.

Pyrophosphate scanning

Pyrophosphate scanning, a nuclear medicine test, is also used to see if there is cardiomyopathy. This scan may help to tell different types of amyloid heart disease apart.

Tissue, Organ, and Bone Marrow Biopsy

A biopsy (sample) of tissue, bone marrow, and/or an affected organ may be needed. This will confirm the amyloidosis and determine the type.

Amyloidosis in areas other than the heart

Many parts of the body can be affected by amyloidosis. Carpal tunnel syndrome in both hands (bilateral) is common. Some have nerve pain in the arms, legs, hands, or feet. Biceps tendon rupture, rotator cuff (shoulder) issues, and erectile dysfunction may happen. Orthostatic symptoms (lightheadedness and other issues when standing up from a chair) can be an issue. Some have intestinal problems, spinal stenosis, kidney disease, enlarged tongue, and bruising around the eyes. In ATTR types, the tendon and spinal issues often show up before heart problems.

Treatment

It's very important to find out what type of amyloidosis is present. The treatment for one type may be different than the treatment for another. Some types look like HCM or congestive heart failure (CHF). However, the treatment for other heart conditions may be harmful to those with amyloidosis. It's important to be sure of the diagnosis before starting treatment.

What is AL Amyloidosis?

AL Amyloidosis (light chain amyloidosis) is the most common type in the US and most often affects males between the ages of 50 and 80. It is caused by a bone marrow disorder and makes abnormal immune system proteins. It can affect most body systems, especially the heart and kidneys, but not the brain.

How is AL Amyloidosis like HCM?

Like HCM, AL Amyloidosis causes thickened left ventricle walls in the heart (LVH)  and heart failure with preserved ejection fraction (HFpEF). Symptoms of AL type are similar to HCM symptoms.

What heart symptoms does AL Amyloidosis cause?

Common heart symptoms in AL include shortness of breath, fatigue, fainting, and abnormal heart rhythms (arrhythmias).

How is AL Amyloidosis Treated?

Two types of treatment are used in AL Amyloidosis. Supportive treatment is for symptoms and organ damage. Source treatment can slow or stop the overproduction of amyloid. Source treatment is more effective if amyloidosis is found early. The US FDA has approved the use of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) for the treatment of adult patients with newly diagnosed AL amyloidosis. Source treatment may include chemotherapy drugs, steroids, and stem cell treatment. A specialist who knows what is safe for amyloidosis patients should order any supportive care.

What is Hereditary Amyloidosis?

Hereditary Amyloidosis is caused by a gene mutation and affects most of the body. Two types of hereditary amyloidosis are ATTR and non-TTR. TTR is short for transthyretin, a liver protein. Most families with hereditary type know they have it because many members have symptoms. Each family can have a certain age of onset, organs affected, and disease progression.

How is Hereditary Amyloidosis like HCM?

Hereditary Amyloidosis can cause heart problems such as irregular heartbeat and heart failure. It is less like HCM than other types, but many of the symptoms are alike. The ATTR type looks more like HCM in the heart than the non-TTR type.

What heart symptoms does Hereditary Amyloidosis cause?

Hereditary type may include heart symptoms. Patients may be tired, lightheaded, or short of breath. They may have swelling, chest pain, and abnormal heart rhythms. Congestive heart failure and AFIB are common in this type.

How is Hereditary Amyloidosis Treated?

In 2019, two drugs were approved by the FDA for ATTR amyloidosis in adults. The first was ONPATTRO (patisiran). This drug works to silence gene expression. The second drug is TEGSEDI which reduces the production of TTR protein. In 2019, VYNDAQEL and VYNDAMAX were approved by the FDA for ATTR cardiomyopathy. As ATTR amyloid is made in the liver, a liver transplant may be needed to slow down the disease. Patients with some genetic variants do better with a liver transplant than others, and this is being studied. In those with heart problems, a liver transplant does not usually improve their heart symptoms. In severe cases, a heart and liver transplant is needed. Ongoing research looking for new therapies gives hope for the future.

                                                                   
What is Wild-type Amyloidosis?

Wild-type ATTR Amyloidosis has no genetic cause, can affect all organs, and is found mostly in the heart and brain. Wild-type is commonly found in men at an average age of 75. It is considered a disease of aging and may affect up to 25% of people by age 85.

How is Wild-Type Amyloidosis like HCM?

Wild-type can cause the heart to become stiff and thick, leading to symptoms and structures that look like HCM. It is generally ATTR-type amyloidosis, and on imaging, the heart can look like an HCM heart.

What heart symptoms does wild-type Amyloidosis cause?

Those with wild-type often have heart symptoms. Patients may be short of breath, lightheaded, and tired. They can have irregular heartbeats and a heart rhythm that is too fast or too slow.

How is Wild-Type Amyloidosis Treated?

The FDA has approved both VYNDAQEL® (tafamidis meglumine) and VYNDAMAX™ (tafamidis) to treat wild-type ATTR in adults. They help to reduce cardiovascular mortality and heart-related hospitalization. Treatment for congestive heart failure (CHF), diuretics, are prescribed to remove excess fluid from the body. The same is true for ATTR. Diuretics help reduce swelling and shortness of breath. For others with CHF, beta-blockers, ACE inhibitors, and calcium channel blockers improve heart symptoms. These drugs can hurt people with ATTR. Research into new treatments is ongoing.