Cardiac amyloidosis is a progressive condition where misshapen proteins build up in the heart muscle, making it thick and stiff, ultimately disrupting the heart’s ability to pump blood effectively throughout the body.

When someone develops cardiac amyloidosis, abnormal proteins called amyloid begin depositing in the spaces between heart muscle cells. These deposits are not supposed to be there, and over time they accumulate and change the heart’s structure. The heart walls become thicker and lose their flexibility, which makes it increasingly difficult for the heart to do its job of pumping blood. The condition gradually worsens, and if left untreated, it can lead to serious complications including heart failure and dangerous heart rhythm problems.

This condition is a leading cause of restrictive cardiomyopathy, which is a type of heart muscle disease where the heart becomes stiff and cannot relax properly between beats. Although cardiac amyloidosis was once considered rare and essentially untreatable, medical advances in recent years have dramatically changed the outlook for people diagnosed with this disease. Better diagnostic tools now allow doctors to identify it earlier, and new treatments can slow its progression and manage symptoms more effectively.

How Common Is Cardiac Amyloidosis

Cardiac amyloidosis is more common than previously thought, largely because it has historically been underdiagnosed. The disease often goes unrecognized because its symptoms can resemble other, more familiar heart conditions. Light chain amyloidosis, one of the main types that affects the heart, occurs in more than 10 individuals per million people each year. The actual number of people living with cardiac amyloidosis may be much higher, as many cases remain undetected until advanced stages.

Certain groups of people face higher risks of developing this condition. Advanced age is a significant risk factor, and the disease is particularly common among older adults. Men are more likely to develop cardiac amyloidosis than women. People of African and Caribbean descent also have elevated risk for certain types of the disease. The condition can run in families in some cases, especially with hereditary forms of transthyretin amyloidosis, where genetic mutations are passed down through generations.

The disease is emerging as an important cause of heart failure and heart rhythm problems, especially in the elderly population. As awareness among healthcare providers increases and diagnostic methods improve, more cases are being identified. This heightened recognition is crucial because early detection leads to earlier treatment, which can significantly improve outcomes and quality of life for those affected.

What Causes This Heart Condition

The root cause of cardiac amyloidosis depends on which type of the disease a person has. The condition results from what doctors call “protein misfolding,” where normally soluble proteins in the bloodstream become insoluble and deposit abnormally in tissues and organs. In the case of cardiac amyloidosis, these misfolded proteins accumulate specifically in the heart, though they may also deposit in other organs like the kidneys, intestinal tract, nerves, and ligaments.

There are two main types of amyloidosis that commonly affect the heart. The first is light-chain amyloidosis, abbreviated as AL, where the “A” stands for amyloid and “L” stands for light chain type. This form involves abnormal production of immunoglobulin light chains, which are proteins normally made by the bone marrow to fight infection. In AL amyloidosis, plasma cells in the bone marrow produce abnormal light chains that clump together and form amyloid deposits. Bone marrow disorders are the underlying cause of this type.

The second major type is transthyretin amyloidosis, known as ATTR. This condition involves a protein called transthyretin, which normally transports thyroid hormone and vitamin A through the bloodstream. The protein is produced in the liver, but for various reasons it can become unstable and misfold. There are two subtypes of ATTR: hereditary (also called variant) ATTR, caused by genetic mutations in the transthyretin gene that are passed down in families, and wild-type ATTR, which occurs due to aging-related changes in the protein without any genetic mutation. Wild-type ATTR is often a disease of older adults and happens when the transthyretin protein becomes unstable simply with age.

Who Is at Higher Risk

Several factors increase the likelihood of developing cardiac amyloidosis. Age plays a significant role, as the risk increases substantially in older adults. This is particularly true for wild-type ATTR amyloidosis, which typically appears in people over 60 and becomes more common with advancing age. The hereditary form of ATTR can appear earlier in life, depending on the specific genetic mutation involved.

Gender matters when it comes to risk. Men are more likely to develop cardiac amyloidosis than women. This difference is especially pronounced with wild-type ATTR amyloidosis, which predominantly affects older men. The reasons for this gender difference are not fully understood, but it is a consistent pattern observed across populations.

Race and ethnicity influence risk as well. People of African descent and those from the Caribbean face higher risk for certain forms of the disease. Specific genetic mutations that cause hereditary ATTR amyloidosis are more common in these populations, though the condition can affect people of any racial or ethnic background.

For AL amyloidosis specifically, having a plasma cell disorder or other bone marrow condition increases risk. These underlying blood disorders can lead to the abnormal production of light chain proteins that eventually form amyloid deposits. People with chronic or infectious diseases may also face elevated risk for developing amyloidosis.

Family history is crucial, particularly for hereditary ATTR amyloidosis. If someone in your family has been diagnosed with this form of cardiac amyloidosis, other family members should be screened. Early diagnosis in family members allows for monitoring and earlier initiation of treatment, which can help reduce the damage to the heart and other organs. Genetic testing can identify whether someone carries the mutations that cause hereditary ATTR, even before symptoms appear.

Recognizing the Symptoms

Cardiac amyloidosis is a progressive condition that typically gets worse over time. In the early stages, symptoms may be subtle or even absent, which is one reason the disease often goes undiagnosed for extended periods. As the condition advances, people begin experiencing symptoms similar to heart failure, and these symptoms become more severe as more amyloid deposits accumulate in the heart.

Shortness of breath is one of the most common symptoms. At first, people may notice they get winded more easily when exercising or climbing stairs. As the disease progresses, breathing difficulties can occur even during normal daily activities like walking across a room. In more severe cases, shortness of breath happens even at rest or when lying down, making it difficult to sleep flat and requiring extra pillows to prop up in bed.

Swelling is another hallmark symptom. Fluid tends to accumulate in the lower parts of the body due to gravity, so people often notice their legs and ankles becoming puffy and retaining fluid. The abdomen can also swell as fluid builds up there. This swelling is usually worse at the end of the day and may improve somewhat after a night of sleep with legs elevated.

Fatigue affects many people with cardiac amyloidosis. This is not just ordinary tiredness that goes away after rest, but a deep, persistent exhaustion that lasts for days. The fatigue results from the heart’s reduced ability to pump blood efficiently, meaning less oxygen reaches muscles and organs throughout the body. People may find they lack energy for activities they used to do easily.

Heart rhythm disturbances are common with this condition. Many people experience palpitations, which feel like the heart is racing, pounding, fluttering, or skipping beats. These sensations may occur during normal daily routines when they shouldn’t be happening. Some people develop atrial fibrillation, an irregular heart rhythm that can increase the risk of stroke and other complications.

Because amyloid often deposits in organs and tissues beyond the heart, people may experience additional symptoms throughout the body. Peripheral neuropathy, which causes tingling, numbness, or pain in the hands and feet, is common. Some people develop dysautonomia, where the autonomic nervous system is affected, leading to lightheadedness, dizziness, or sudden drops in blood pressure when standing up or changing position. Digestive symptoms like diarrhea, nausea, poor appetite, or unexplained weight loss may occur if amyloid affects the gastrointestinal tract. Other possible symptoms include easy bruising, purple spots around the eyelids, an enlarged tongue, unexplained back pain, or pain and numbness in the arms or hands from carpal tunnel syndrome.

Ways to Prevent or Reduce Risk

For most types of cardiac amyloidosis, there are no specific prevention strategies because the underlying causes involve either genetic factors or age-related changes that cannot be avoided. However, there are important steps that can reduce the impact of the disease and improve outcomes, especially when the condition runs in families.

If you have hereditary ATTR amyloidosis in your family, the most important preventive step is screening. Family members of someone diagnosed with hereditary ATTR should undergo genetic testing to determine whether they carry the mutation. Early identification allows for close monitoring even before symptoms develop. If the disease is detected early through regular heart evaluations, treatment can begin sooner, potentially slowing disease progression and lessening the damage to the heart and other organs.

For people already diagnosed with cardiac amyloidosis, making heart-healthy lifestyle choices can help manage symptoms and support overall cardiovascular health. While these changes do not reverse amyloid deposits, they can improve quality of life and help the heart function as well as possible given the circumstances. This includes eating a balanced, nutritious diet, staying as physically active as your symptoms allow under medical supervision, managing stress, and getting quality sleep.

Working closely with your healthcare team is essential for optimal management. Regular monitoring allows doctors to track disease progression and adjust treatments as needed. Because cardiac amyloidosis can affect multiple body systems, coordination among different specialists is often necessary. Alerting your care team to any new symptoms, whether they involve the heart or other organs, ensures that all aspects of the disease are addressed.

How the Disease Changes Heart Function

Understanding what happens inside the heart when amyloid deposits helps explain why symptoms develop and why treatment is so important. Cardiac amyloidosis is an infiltrative disease, meaning that foreign material infiltrates and accumulates where it does not belong. In this case, amyloid fibrils made of misfolded proteins deposit in the extracellular spaces between heart muscle cells. These deposits are insoluble, meaning they do not dissolve, and they gradually accumulate over time.

As amyloid builds up in the heart tissue, it causes the heart walls to thicken. This thickening is particularly noticeable in the left ventricle, which is the heart’s main pumping chamber. The amyloid infiltration reduces the heart’s compliance, which is its ability to relax and expand. A normal heart muscle is flexible and elastic, allowing it to fill with blood easily during the relaxation phase between beats. When amyloid makes the heart stiff, it cannot relax properly or fill with enough blood.

This stiffness leads to diastolic dysfunction, where the heart has trouble filling with blood during the diastolic phase. Because less blood enters the heart, less blood gets pumped out to the body with each heartbeat. The heart tries to compensate by beating faster or with more force, but these efforts strain the already compromised heart muscle. Over time, this leads to heart failure with preserved ejection fraction, where the heart’s squeezing ability may initially remain relatively normal but the filling problem causes all the symptoms of heart failure.

The amyloid deposits do not just affect the heart muscle itself. They can infiltrate the heart’s electrical conduction system, disrupting the normal electrical signals that coordinate heartbeats. This interference can cause conduction system disease, where electrical signals move too slowly through the heart. It can also trigger various arrhythmias, including atrial fibrillation, slow heart rates called bradycardia, or fast abnormal rhythms from the ventricles called ventricular tachycardia. These rhythm problems can be dangerous and sometimes require treatment with medications or devices like pacemakers.

The changes to heart structure and function also affect blood flow. Reduced cardiac output means that organs throughout the body receive less oxygen and nutrients. The kidneys, which depend on adequate blood flow to filter waste from the blood, can become impaired, sometimes leading to cardiorenal syndrome where heart and kidney problems worsen each other. Fluid backs up in the circulatory system because the heart cannot pump it forward effectively, causing the swelling seen in the legs, abdomen, and sometimes lungs.