Cardiac Amyloidosis

Cardiac amyloidosis is a serious but increasingly treatable heart condition where misshapen proteins build up in your heart muscle, making it thick and stiff. Once considered untreatable, recent advances in diagnosis and therapy have transformed the outlook for people with this disease.

What Is Cardiac Amyloidosis?
Types of Cardiac Amyloidosis
Signs and Symptoms
Causes and Risk Factors
Possible Complications
How Doctors Diagnose This Condition
Treatment Options
Living With Cardiac Amyloidosis
Outlook and Prognosis

What Is Cardiac Amyloidosis?

Cardiac amyloidosis is a condition where abnormal proteins called amyloids build up in your heart muscle^[1]. These proteins are normally found in your bloodstream, but for various reasons they become misshapen, or misfolded, and form deposits in your body’s organs and tissues^[3].

When these protein deposits accumulate in your heart, they make the walls of your heart thicken and become stiff^[1]. This stiffness forces your heart to work much harder to pump blood through your body. Over time, the extra effort weakens and damages your heart^[1].

Cardiac amyloidosis is a leading cause of restrictive cardiomyopathy, which is a condition where the heart muscle becomes stiff and cannot relax properly between beats^[2]. The condition typically presents with rapidly progressive difficulty in the heart’s ability to fill with blood properly^[2].

If you have cardiac amyloidosis, there is a good chance you have amyloid buildup in other areas of your body too, such as your kidneys, intestinal tract, or nerves^[3]. However, buildups in your heart tend to cause the most severe health problems^[1].

Types of Cardiac Amyloidosis

While there are more than 20 proteins that can form amyloid, only three main types actually affect the heart^[3]. The two most common types of amyloidosis that can affect your heart are light-chain amyloidosis and transthyretin amyloidosis. Together, these account for more than 95% of all clinical cardiac amyloidosis cases^[5].

Light-chain amyloidosis (AL) occurs when abnormal proteins come from your bone marrow^[1]. This type is also called AL amyloidosis, where the “A” stands for amyloid and the “L” stands for light chain type^[3]. These are proteins normally made to fight infection, but in AL amyloidosis, abnormal cells in your bone marrow produce too many of these proteins^[3]. Light-chain amyloidosis affects more than 10 individuals per million annually^[2].

Transthyretin amyloidosis (ATTR) occurs when abnormal transthyretin proteins come from your liver^[1]. Transthyretin is a protein that normally transports thyroid hormone and vitamin A in your blood^[2]. There are two subtypes of ATTR amyloidosis^[1]:

Hereditary (variant) ATTR is caused by genetic mutations in the gene that produces the transthyretin protein^[11]
Wild-type ATTR occurs when the transthyretin protein becomes unstable due to aging-related changes^[11]

Signs and Symptoms

Cardiac amyloidosis is a condition that gets progressively worse over time^[1]. In the early stages, symptoms may be subtle or even absent^[19]. The symptoms can also match those of more common heart conditions, which is part of what makes cardiac amyloidosis challenging to diagnose^[19].

The condition can lead to heart failure symptoms that become more severe with time. Common symptoms include^[1]:

Shortness of breath when you are active or at rest
Shortness of breath when lying down^[19]
Swelling in your belly and legs
Fatigue that lasts for several days
Extreme tiredness or weakness^[19]
Heart palpitations during your normal routine

Earlier in the disease, you may experience primarily heart rhythm problems, such as palpitations or atrial fibrillation, which is an irregular heart rhythm^[15]. Later, the most common symptom is difficult or labored breathing, especially with physical activity. In more severe cases, you may even have trouble breathing at rest^[15].

Because amyloid can build up elsewhere in your body, you may have other symptoms as well, such as^[1]:

Peripheral neuropathy, which causes tingling or numbness in your hands or feet
Dysautonomia, which causes lightheadedness, dizziness, or low blood pressure with changes in position
Poor appetite^[19]
Diarrhea or constipation^[19]
Purple spots around the eyelids^[19]
Easy bruising^[19]
A large tongue^[19]

Causes and Risk Factors

The cause of cardiac amyloidosis depends on the type of amyloidosis you have^[1]. Bone marrow disorders cause AL amyloidosis. A change in the transthyretin gene or aging-related changes cause ATTR^[1].

Several risk factors can increase the likelihood of developing amyloidosis^[5]:

Advanced age
Male gender
Black race or people of Caribbean and African descent^[19]
Coexisting chronic or infectious diseases
Family history, since some types of amyloidosis are hereditary
Plasma cell disorders^[2]
Specific genetic mutations^[2]

Cardiac amyloidosis used to be considered an ultra-rare disease, but it is more common than originally thought due to underdiagnosis^[13]. Amyloid cardiomyopathy is emerging as an important and often underdiagnosed cause of heart failure and cardiac rhythm problems, especially in older adults^[5].

Possible Complications

Cardiac amyloidosis changes your heart’s structure, and it can disrupt its electrical system^[1]. The infiltrative process in the heart leads to progressive dysfunction of the cardiac muscle, while the heart’s conduction system is also affected^[5].

Complications of cardiac amyloidosis include^[1]:

Arrhythmias, such as atrial fibrillation, bradycardia, and ventricular tachycardia
Bundle branch block, a condition where the heart’s electrical signals are delayed or blocked
Cardiorenal syndrome, when heart and kidney problems affect each other
Heart failure
Restrictive cardiomyopathy
Stroke

How Doctors Diagnose This Condition

Healthcare providers diagnose cardiac amyloidosis through various tests^[1]. Cardiac amyloidosis is part of a systemic disease, meaning it affects your whole body. So, providers look at the big picture. In addition to examining your heart closely, they also look for symptoms elsewhere in your body^[1].

Your provider may first suspect this condition based on your symptoms, medical history, and physical exam findings^[1]. They will then use several tests to confirm it or rule it out. Heightened awareness of amyloid cardiomyopathy, the assessment of heart-related and non-heart-related symptoms, and the use of advanced imaging are the mainstays of diagnosis^[5].

Tests may include^[1]:

Blood and urine tests to check for amyloid proteins and markers of heart function
Electrocardiogram (EKG) to check your heart’s electrical activity
Echocardiogram with strain to look for thickened heart muscle
Cardiac MRI to distinguish cardiac amyloidosis from other causes of cardiomyopathy
Nuclear imaging tests, including “amyloid” scans (also called bone scintigraphy), to check for amyloid protein buildup in your heart^[5]
Biopsy to check for amyloids in your heart or elsewhere
Genetic testing to check for genetic changes as the cause of amyloidosis

In order to establish a diagnosis of amyloid, you must first have what is called a tissue biopsy^[7]. Some part of your body is sampled and found to have amyloid deposits. That can be from the fat, bone marrow, kidney, heart, or other parts of your body^[7]. Once the tissue has been examined and found to have amyloid, doctors need to know what type of protein is making up the abnormal amyloid deposits. Pathologists use a technique called mass spectrometry to determine the type^[7].

Your healthcare provider will look for “red flags” that point to cardiac amyloidosis. In addition to heart failure symptoms, these warning signs include^[1]:

Atrial fibrillation
Thickness in the wall of your left ventricle
Conduction system disease
Elevated cardiac biomarkers

Treatment Options

The most important thing to know is that treatment for cardiac amyloidosis depends completely on which type you have^[7]. Treatment options were previously limited and consisted predominantly of managing symptoms and disease-related complications^[8]. However, the last decade has seen significant advances in disease-modifying therapies^[8].

The good news is that recent therapies have improved outcomes for people with this condition^[1]. Treatments include medications to slow protein buildup and manage your symptoms. Early diagnosis and treatment improve your outlook^[1].

Management includes disease-modifying therapy and heart failure therapy, while various novel targeted treatments are under investigation for delaying disease progression and further affecting clinical outcomes^[5].

Treatment for AL Amyloidosis

The mainstay of AL amyloidosis treatment is chemotherapy with specific drugs and, when feasible, stem cell transplantation^[8]. The treatment uses chemotherapy and immunotherapy to target the plasma cells and keep them from producing abnormal light chains^[18]. Proteasome inhibitor-based chemotherapy with daratumumab is commonly used^[8]. Patients with this type of amyloidosis may also undergo stem cell transplants in some instances^[18].

Treatment for ATTR Amyloidosis

For ATTR amyloidosis, treatment works to keep the liver from producing easily breakable proteins, usually in the form of medications^[18]. The stabilizer tafamidis is the only U.S. Food and Drug Administration-approved treatment for ATTR amyloidosis^[8]. It was approved in 2019 as the first disease-modifying therapy for use in adults with either hereditary or wild-type cardiac ATTR, and was found to significantly reduce disease progression and mortality^[12].

Promising novel therapies on the horizon target various points in the ATTR amyloidosis disease process^[8]. These include:

Stabilizers like tafamidis and acoramidis, which bind to the transthyretin protein and prevent the formation of amyloid^[12]
Silencers, which are transthyretin gene silencing agents that prevent the liver from making the transthyretin protein^[8]
Depleters, which work to remove existing amyloid deposits^[12]
Anti-transthyretin antibodies and treatments to break down amyloid^[8]

Liver transplants are used in some cases for hereditary ATTR amyloidosis^[18].

Managing Heart Failure Symptoms

Because cardiac amyloidosis can cause a number of heart-related symptoms, those with the condition may also benefit from other types of treatment^[18]. This may include:

Medications such as diuretics to help reduce fluid buildup and swelling^[15]
Devices to correct the heart’s rhythm^[18]
Implementation of lifestyle changes^[18]

Advanced Interventions

For end-stage cardiac amyloidosis, advanced interventions may need to be considered, including heart transplant, heart-kidney transplant, and, for hereditary ATTR amyloidosis, heart-liver transplantation^[8].

Despite the evolution of treatment options, cardiac amyloidosis management remains complex due to patient frailty and potential side effects or intolerance with advanced cardiac disease^[8]. This is particularly relevant for those with AL amyloidosis, when active teamwork between the blood cancer specialist and the heart doctor is critical for treatment success^[8]. Often, referral to an expert center is necessary for timely diagnosis, initiation of treatment, and participation in clinical trials^[8].

Living With Cardiac Amyloidosis

Finding out that you or someone you care about has cardiac amyloidosis can be worrying^[14]. While it’s good to do your own research, make sure you know what type of cardiac amyloidosis you have and try to stick with trusted sources of information. Your care team is in the best position to answer your questions^[14].

Many people want to know how the disease will progress, as well as how it might affect their day-to-day life and how long they will live. It’s often very individual and depends, in part, on the type of amyloidosis someone has and the extent to which amyloid proteins have built up in and around the heart^[14].

Because amyloidosis may affect several organs in your body, there might be changes in your life that are necessary and unavoidable^[20]. If you are receiving treatment, these changes may be complemented by additional adjustments that arise from the treatment or its side effects^[20].

Self-Care and Lifestyle Adjustments

In addition to medication, a few healthy lifestyle habits can help you manage your disease and feel better^[15]:

Monitor fluid and salt intake: Fluid buildup is common in cardiac amyloidosis. Your doctor might recommend reducing your intake of high-sodium foods and monitoring how much water you drink. Talk to your doctor to get personalized recommendations about your fluid intake and the use of diuretics^[15].
Weigh yourself regularly: Daily weight monitoring can help detect fluid buildup early^[15].
Stay as active as possible: Talk with your doctor before starting any exercise regimen. Walking, yoga, and light weights under medical supervision may be a good place to start^[17].
Eat a balanced diet: Focus on nutrient-dense foods and maintain adequate protein intake. If you’re struggling with appetite or weight loss, consider eating small amounts every 2-3 hours^[17].

Managing Symptoms

If you are experiencing musculoskeletal issues like unexplained back pain, or pain, tingling, or numbness in your arms or hands, or stomach issues like diarrhea, nausea, or weight loss, be sure to tell your care team. They can refer you to and coordinate with other specialists if needed^[14].

Because cardiac amyloidosis can affect many parts of your body, you may see several specialists^[14]. As with any heart condition, it’s important to make heart-healthy choices, work to lower stress, and get quality sleep. Talking with other people who have the condition may help too^[14].

Work and Daily Activities

You may choose to continue working after receiving your diagnosis, however, you should keep in mind that it may be necessary to take time off work for tests and treatments^[20]. It will also depend on the type of employment you have. Many employers may be open to adopting a more flexible approach to working conditions should that be required^[20].

Family Considerations

If you have an inherited form of cardiac amyloidosis, ask your care team about who in your family should be screened to diagnose, monitor, and start treatment as early as possible and help lessen the damage^[14].

Outlook and Prognosis

In the past, cardiac amyloidosis was essentially considered untreatable. If you were diagnosed with the condition back then, treatment may have simply included medications or other interventions to relieve symptoms^[18]. Today, though, treatment is very different and focuses on the underlying cause^[18].

Innovations and advancements in what we know about the condition and how to prevent its negative effects have greatly changed the prognosis for those who are diagnosed with cardiac amyloidosis^[18]. Advances in cardiac imaging and improved awareness among physicians have resulted in earlier diagnoses^[8].

Your specific prognosis will vary depending on many factors, including how well the interventions to treat the condition work^[18]. In general, ATTR amyloidosis, which makes up most cases of cardiac amyloidosis, is less severe and more treatable than AL amyloidosis. It is often a disease of older adults^[14].

Prognosis is generally worse in AL amyloidosis due to its rapid progression, while ATTR amyloidosis follows a slower but still clinically significant course^[2]. Early recognition remains essential for the proper management of patients with amyloid cardiomyopathy^[5]. Early diagnosis and treatment improve your outlook^[1].