Cardiac Amyloidosis: Causes, Symptoms, And Treatment

According to research, cardiac amyloidosis affects 17 per 100,000 people every year! Though the condition is uncommon, it can seriously affect heart function and overall health.  

Cardiac amyloidosis happens when misfolded clumps of proteins called amyloid build up in the heart. Over time, these extracellular deposits cause the myocardium (cardiac muscle) to stiffen and weaken cardiac function.  Thus, the heart struggles to pump blood properly. 

Fun fact: The word “amyloid” is derived from the Latin word “amylum,” which means “starch.” When scientists first observed amyloid proteins under the microscope, they thought the deposits looked like starch droplets.  Later, they discovered that amyloid is made of misfolded proteins, not starch. These proteins clump together and can build up in different organs, affecting their function.

The symptoms of cardiac amyloidosis are often mistaken for other conditions, such as heart failure or hypertrophic cardiomyopathy. Thus, the condition is frequently misdiagnosed or only detected once the disease has advanced. Although there is no cure, various treatment approaches can address the underlying cause and help improve overall quality of life.

There are different types of amyloidosis, and some are more likely to affect the heart than others. So, read on to explore what causes cardiac amyloidosis, its symptoms, how doctors diagnose it, and the treatment options available. 

What Is Cardiac Amyloidosis?

Cardiac amyloidosis, sometimes called “stiff heart syndrome,” is a condition where deposits of abnormal proteins called amyloid accumulate in different parts of the heart. Amyloid deposits consist of misfolded proteins that the body cannot break down or remove properly. 

Over time, they accumulate between the muscle cells in the heart’s walls. This buildup makes the heart walls thick, stiff, and less able to pump blood efficiently.

For the heart to pump oxygen-rich blood to the rest of the body, it must relax and contract properly. In cardiac amyloidosis, the stiffened heart walls lose flexibility. It is thus difficult for the heart to fill with blood during relaxation (called diastole) and pump effectively during contraction (called systole).

Most commonly, cardiac amyloidosis occurs in two ways: light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR).

• In AL amyloidosis, plasma cells and proteins like immunoglobulin light chains replicate themselves in an unregulated manner, and deposit in the heart muscle.

• Whereas in ATTR amyloidosis, transthyretin (TTR) protein destabilizes and breaks up into monomers. These TTR monomers deposit in different parts of the heart, disrupting its normal structure and function. This causes problems such as heart failure, irregular heartbeat, and blood flow issues.

If left untreated, cardiac amyloidosis can cause valvular disease, progressive heart failure, arrhythmias, reduced cardiac output, or sudden cardiac death. However, with early diagnosis and proper treatment, patients can manage the symptoms and improve their quality of life. 

AL Amyloidosis and Cancer: Are They Connected?

Many people ask, “Is amyloidosis cancer?” The answer is no. However, AL amyloidosis is linked to certain blood cancers, such as multiple myeloma, which affect the bone marrow. Treatments for AL amyloidosis often include chemotherapy and immunotherapy to target the abnormal plasma cells producing the amyloid proteins.

Read More: Cardiovascular Disease: Types, Causes & Symptoms

What Are The Different Types Of Amyloidosis?

Amyloid protein buildup can occur in different tissues and organs and disrupt the working of the heart, liver, spleen, kidneys, gastrointestinal tract, and nervous system. Some types of amyloidosis are inherited, whereas others develop over time or occur due to other diseases like cancer. 

The types of amyloidosis are:

AL (Light Chain) Amyloidosis

AL amyloidosis happens when plasma cells which are immune cells in the bone marrow, malfunction and produce excessive light chain components of the immunoglobulin protein (or antibodies). These light chains misfold and clump together, forming amyloid deposits in various organs, including the heart. 

The amyloid deposits thicken the walls of the heart, making it weak. This form of amyloidosis is considered the most severe when it affects the heart, often leading to heart failure if not treated quickly.

ATTR Amyloidosis

ATTR cardiac amyloidosis is caused by the buildup of a protein called transthyretin (TTR). The liver makes transthyretin, which usually helps transport vitamin A and thyroxine, a thyroid hormone, through the blood. When this protein becomes unstable, it dissociates into monomers, which is required for the formation of amyloid protein. Since it mainly affects the heart, people may have heart problems and other diseases like carpal tunnel syndrome, cervical stenosis or neuropathy. 

• Hereditary (hATTR) or mutant ATTR amyloidosis is caused by a genetic mutation that produces faulty transthyretin proteins. It is caused due to the TTR gene mutation. Family members inherit it. Most commonly, it affects the heart and nerves.
• Wild-type ATTR amyloidosis (ATTRwt) is acquired and age-related but does not involve any inherited genetic mutations. It is common in men over the age of 60 and affects the heart and tendons. 

ATTR CM symptoms include fatigue, shortness of breath, swelling in the feet, changes in heart rhythm, dizziness or fainting, and nausea. People may also present with carpal tunnel syndrome, often 8-10 years before heart-related symptoms develop.  

Note: Nausea is more common in systemic amyloidosis with gastrointestinal involvement and is not typically a primary symptom of cardiac amyloidosis.

Secondary (AA) Amyloidosis

AA amyloidosis, a rare disorder, is linked to chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, or chronic infections like tuberculosis. In this condition, the body produces excess amounts of a protein called serum amyloid A (SAA) due to prolonged inflammation or infection. 

Chronic inflammation causes the SAA proteins to misfold and form amyloid deposits or fibrils in various organs. Although AA amyloidosis typically affects the kidneys, it can also impact the heart, liver, stomach, and spleen. 

How Does Cardiac Amyloidosis Affect The Body?

When amyloid proteins build up in the heart, they cause the heart walls to become stiff and thick. This stiffness, particularly of the ventricles, makes it harder for the heart to pump blood efficiently to the rest of the body. Over time, the heart weakens and struggles to keep up with the body’s demands, leading to cardiac failure.

Congestive heart failure is a major effect of cardiac amyloidosis. Symptoms include fatigue, shortness of breath (dyspnea) during activity or at rest, rapid or irregular heartbeat, and swelling (edema) in the legs and ankles due to fluid buildup.

Cardiac amyloidosis can also cause arrhythmias or irregular heartbeats. It makes people feel dizzy, lightheaded, short of breath, and fatigued. It may also cause fainting spells. In some cases, rapid or chaotic heart rhythms can be dangerous.

Cardiac amyloidosis can also affect the blood vessels. Atrial amyloidosis may cause issues in the upper heart chambers, leading to blood clots and increasing the risk of stroke. Some patients may also experience angina (chest pain) or even heart attacks (myocardial infarction) due to poor blood flow.

Cardiac amyloidosis may also be associated with non-cardiac symptoms, such as: 

• Bilateral carpal tunnel syndrome, 
• Low blood pressure upon standing, 
• Enlarged tongue (AL amyloidosis), 
• Purple discoloration around eyelids (AL amyloidosis), 
• Lumbar spinal stenosis, and 
• Poor appetite.

What Are The Symptoms Of Cardiac Amyloidosis?

Symptoms often develop gradually due to the progressive accumulation of amyloid proteins in the heart muscle and may be mistaken for other heart problems. So, when to suspect cardiac amyloidosis? You should suspect it if these symptoms persist despite standard heart treatments or have no clear cause. They include the following:

Heart-related Symptoms

• Shortness of breath, even during light activity or while lying down
• Irregular heartbeat or palpitations
• Chest pain or a feeling of pressure

Fluid-related Symptoms

• Swelling in the legs, ankles, or abdomen
• Weight gain from fluid retention

Other Symptoms

• Dizziness or fainting, especially when standing
• Swollen liver or enlarged neck veins
• Kidney problems (such as protein in the urine or impaired kidney function)

In ATTR-CM (transthyretin amyloid cardiomyopathy), some people also experience carpal tunnel syndrome, often appearing 8–10 years before any heart symptoms begin. This shows how seemingly unrelated symptoms may be early warning signs.

How Is Cardiac Amyloidosis Diagnosed?

Doctors use different tests to diagnose cardiac amyloidosis. Since symptoms can look like other heart or systemic diseases, it is important to diagnose them early. If someone has unexplained heart problems, swelling, fatigue, or nerve issues, especially in the backdrop of a known family history of amyloidosis, doctors may check for amyloid buildup.

1. Physical Examination

During a thorough physical exam, a doctor will look for the following signs:

• Irregular heartbeat, which is detected by an irregular pulse
• Muffled or distant heart sounds, which may indicate thickening of the muscle due to amyloid deposits
• Prominent veins in the neck when the patient is sitting up at a 45-degree angle, which indicates increased central venous pressure
• Swelling in the legs and ankles due to fluid buildup
• Bloating of the abdomen due to accumulation of fluid (also known as ascites)
• Numbness or tingling in the limbs
• Easy bruising or discoloration around the eyes, which indicates fragile blood vessels due to amyloid buildup
• Enlargement of the tongue (macroglossia)
• Carpal tunnel syndrome due to thickening of wrist flexor tendons

2. Blood And Urine Protein Tests

Blood and urine protein tests help detect the presence of amyloid proteins and monoclonal light chains (also called Bence Jones proteins) in the body. 

Elevated levels of heart biomarkers, such as troponins and natriuretic peptides, due to cardiac malfunction, may indicate cardiac amyloidosis. 

These tests can also check how well your organs, like the kidneys and liver, are working. In kidney function tests, abnormal serum creatinine and blood urea nitrogen levels may indicate amyloidosis. Also, liver function tests may reveal high levels of alkaline phosphatase and transaminases, which indicates liver dysfunction. 

3. Imaging Tests

Several imaging methods help doctors visualize the heart and identify amyloid deposits. 

• An echocardiogram (EKG) uses ultra-high-frequency sound waves to create “images” of the heart. Doctors can see how the sound waves are reflected off the heart muscles. Thickened walls or stiff heart movement may suggest cardiac amyloidosis.

• Magnetic resonance imaging (MRI) uses a powerful magnet and computer processing to provide detailed pictures of heart tissue. It helps doctors spot abnormal thickening and stiffness in the heart. 

• In nuclear imaging (or scintigraphy), a small amount of radioactive material, called a tracer, is injected into the body. It attaches to amyloid deposits, making them visible on a special gamma camera because they emit gamma rays. 

4. Tissue Biopsy

A biopsy involves taking a small sample of tissue, usually from the heart, abdominal fat, or bone marrow. The tissue is stained with a special dye called Congo red and examined under a microscope to confirm the presence of amyloid deposits. Under polarized light, the amyloid protein appears green.  This is one of the most accurate ways to diagnose amyloidosis.

5. Genetic Testing

If a doctor suspects hereditary amyloidosis, genetic testing is recommended. This test looks for changes in the transthyretin (TTR) gene, which can cause the protein to misfold and form harmful amyloid deposits.

Identifying a TTR mutation helps doctors choose the most appropriate treatment and lets family members understand their own potential risk. Early testing can also lead to earlier monitoring or treatment of relatives who may carry the mutation.

Is There A Cure Or Treatment For Cardiac Amyloidosis?

There is no cure for amyloidosis, but treatments can help manage the disease and its symptoms. If amyloidosis is discovered early, long-term damage can be prevented. However, late diagnosis can cause permanent heart damage and can only be repaired by a heart transplant. The treatment options for cardiac amyloidosis include:

1. Medications

Several medications can help manage cardiac amyloidosis and its symptoms:

• Tafamidis: It is often prescribed for ATTR amyloidosis. It stabilizes the transthyretin (TTR) protein and prevents it from misfolding and forming harmful deposits in the heart.
• Diuretics: Furosemide and spironolactone help the body get rid of excess fluid. They reduce swelling in the legs, ankles, and abdomen. They also ease breathing difficulties by lowering fluid buildup around the lungs, which is a common symptom of heart failure. However, diuretics cannot be used if the patient has severe kidney disease.
• Heart Medications: Depending on the condition, drugs like beta-blockers (carvedilol, metoprolol) and blood pressure medications (lisinopril, losartan) may be used to help manage heart failure and irregular heart rhythms.
• Chemotherapy: For AL amyloidosis, chemotherapy is used to reduce or eliminate the abnormal production of light chain proteins by the plasma cells in the bone marrow, reducing the deposition of amyloid proteins.

2. Liver Transplant (for hATTR Amyloidosis)

For patients with hereditary ATTR amyloidosis, a liver transplant may be an option. In this condition, the liver produces a faulty form of the transthyretin protein. Thus, replacing it with a healthy donor liver can stop the production of abnormal proteins. This approach slows or even stops disease progression in some cases.

3. Lifestyle Changes

Besides medications, daily habits can make a big difference in managing cardiac amyloidosis and reducing symptoms. These lifestyle adjustments can also improve the patient’s symptoms and quality of life: 

• A low-sodium diet, i.e. limiting salt intake, can help reduce fluid retention, swelling, and increased blood pressure.
• Some patients may need to monitor their fluid intake, especially if they have symptoms of heart failure.
• Moderate physical activity, like walking or swimming, can improve heart strength and circulation. These activities should be discussed with a doctor. 
• Healthy weight management can reduce the burden on the heart and enable early detection of fluid retention.
• Caffeine and alcohol can strain the heart and worsen symptoms.  Hence, they should be avoided.

4. Supportive Care

Supportive care in cardiac amyloidosis focuses on enhancing comfort, quality of life, and emotional well-being. In advanced cases, oxygen therapy may help relieve breathing difficulties caused by heart failure. Additionally, emotional support and counseling help in managing the stress and psychological challenges associated with the condition. Providing holistic care ensures patients receive both physical relief and emotional reassurance as they navigate their diagnosis.

Read More: How to Improve Heart Health Quickly and Naturally

Taking Control Of Cardiac Amyloidosis

Cardiac amyloidosis is a serious condition that affects the heart’s ability to pump blood properly. It happens when amyloid proteins build up in the heart, making it stiff and weak. The associated symptoms, like shortness of breath, swelling, and fatigue, can make daily life difficult. 

Because the condition is hard to diagnose due to its slow onset and similarity to other heart diseases, early testing is important. Moreover, medications, lifestyle changes, and, in some cases, transplants can help manage symptoms and improve the quality of life. 

If someone you love is living with a heart condition, knowing how to respond in a crisis is just as important as daily care. Consider enrolling in an Advanced Cardiac Life Support (ACLS) course to learn how to manage emergencies confidently. It’s a valuable step for caregivers, family members, and healthcare providers alike.

FAQs

1. What is the life expectancy of someone with amyloidosis of the heart?

Life expectancy depends on the type and severity of cardiac amyloidosis. Without treatment, it may be six months to a few years. With new treatments, some people live much longer. Early diagnosis, proper care, and following a doctor’s advice can improve survival and overall quality of life.

2.  What can trigger amyloidosis?

Several factors can trigger this amyloidosis. Genetic mutations, particularly in the transthyretin gene, can cause hereditary forms of amyloidosis. Chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, often lead to AA amyloidosis, where the serum amyloid A protein misfolds and deposits in organs. Additionally, long-lasting infections and certain cancers, like multiple myeloma, can also contribute to the development of amyloidosis. It is also more common in men over 50 than women. It is also more prevalent in countries like Portugal, Japan, and Sweden. A specific mutation affects about 4% of Black people of West African descent. Long-term dialysis also increases the risk.

3. What is the earliest symptom of amyloidosis?

Early symptoms depend on the affected organs. In cardiac amyloidosis, shortness of breath, fatigue, and swelling in the legs may appear first. Other common symptoms include numbness, weight loss, or trouble swallowing. Many symptoms seem mild at first, so diagnosis is often delayed.

4. What is end-of-life cardiac amyloidosis?

End-of-life cardiac amyloidosis is the final stage of the disease, where the heart becomes too weak to pump properly. Severe heart failure, low blood pressure, and fluid buildup occur. Breathing becomes difficult, and the person feels very tired. Comfort care focuses on easing symptoms. Doctors and caregivers provide support to ensure a peaceful passing.