Comprehensive Guide to Cardiac Amyloidosis

Cardiac amyloidosis occurs when abnormal proteins accumulate in the heart muscle, leading to potential arrhythmias and heart failure. Because heart failure has many causes, it can take years to diagnose. The complications of cardiac amyloidosis can be life-threatening, and close follow-up and treatment with a cardiologist (medical doctor specializing in conditions affecting the heart) is important to manage the condition.

This article will discuss the causes and types of cardiac amyloidosis and its symptoms, complications, and management.

Protein Buildup in Cardiac Amyloidosis

Cardiac amyloidosis is a type of infiltrative cardiomyopathy, a heart muscle disease caused by substance accumulation. In the case of cardiac amyloidosis, specific proteins accumulate in the heart muscle. These proteins are abnormally folded and deposit in the heart, leading to scarring.

The protein buildup can interfere with the heart's normal conduction system that's responsible for generating heartbeats, leading to abnormal heart rhythms called arrhythmia. It can also lead to heart failure by preventing the heart from pumping blood to the rest of the body efficiently.

Overall risk factors for cardiac amyloidosis include amyloidosis affecting family members, history of thyroid disease, and being over 60 years old.

Types of Cardiac Amyloidosis

Cardiac amyloidosis is classified into two main types based on the type of misfolded protein: Light chain amyloidosis and transthyretin amyloidosis.

Light Chain Amyloidosis

Light chain amyloidosis, also called AL amyloidosis, occurs when misfolded light chain proteins deposit in various organs. Light chains are a type of antibody created by plasma cells, which come from bone marrow.

While light chains are essential to the function of the immune system, problems arise when plasma cells go unchecked and create too many light chains or abnormal light chains. These can deposit in the heart and other organs, leading to specific symptoms and organ dysfunction.

Risk factors for AL amyloidosis include a history of plasma cell disorders, such as multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS).

Transthyretin Amyloidosis

In transthyretin amyloidosis, also known as ATTR amyloidosis, a misfolded protein called transthyretin deposits in the heart muscle. Transthyretin is a protein normally made by the liver involved in the body's transport of thyroid hormone and Vitamin A.

There are two subtypes of ATTR: hereditary and wild-type. In hereditary ATTR, a genetic mutation makes the protein more prone to fold and, thus, deposit in tissues, typically the heart and nerves. It's hereditary as the genetic mutation is passed down in the genes. In wild-type ATTR (previously called senile amyloidosis), on the other hand, there is no genetic mutation. Instead, the protein deposits in the heart over a period of decades. Wild type ATTR is generally seen in people older than 70 years.

Warning Signs of Cardiac Amyloidosis

Cardiac amyloidosis is often diagnosed after several years of experiencing heart failure symptoms, including:

• Fatigue
• Shortness of breath
• Exercise intolerance (reduced capacity for exercise)
• Swelling of the lower extremities and abdomen
• Difficulty lying flat
• Waking up at night short of breath
• Heart palpitations
• Fainting
• Gastrointestinal (GI) symptoms such as feeling full or nausea

It's important to note that these symptoms are not specific to cardiac amyloidosis; other types of heart failure can cause them. This is why diagnosis can be delayed. A cardiologist can investigate these symptoms and help determine the underlying cause. In addition, people with cardiac amyloidosis may be intolerant of common heart failure therapies and experience blood pressure drops with symptoms when taking these medications.

Other Associated Signs and Symptoms

Depending on the other organs affected by amyloidosis, additional symptoms can include:

• Tongue enlargement
• Dark pigmentation or bruising around the eyes
• Nerve problems such as carpal tunnel syndrome
• Kidney problems, from protein in the urine to kidney failure
• Enlarged liver

Having these signs in combination with heart failure should raise suspicion of cardiac amyloidosis.

Is Cardiac Amyloidosis Life-Threatening?

Amyloidosis that involves the heart is serious and may be life-threatening due to heart failure and arrhythmias leading to sudden cardiac death.

Untreated AL cardiac amyloidosis is associated with six-month mortality. In ATTR amyloidosis, median survival after diagnosis ranged from 2.5 to 3.6 years. However, newer techniques to diagnose amyloidosis, as well as an increased appreciation of amyloidosis as a cause of heart failure can lead to an earlier diagnosis. This may ultimately help to improve outcomes as newer treatments can help slow the accumulation of misfolded proteins.

Diagnosis of Cardiac Amyloidosis

The following tests can help your cardiologist arrive at a diagnosis of cardiac amyloidosis:

• Blood tests, including N-terminal proB-type natriuretic peptide (NT-proBNP) and troponin, kidney and liver function, and light chains
• Urine tests to look for kidney involvement and presence of light chains
• Electrocardiogram
• Bone marrow biopsy in cases of suspected AL amyloidosis
• Heart imaging tests including echocardiogram (heart ultrasound), cardiac MRI, and nuclear imaging tests (pyrophosphate scan)
• Biopsy (removing a sample tissue for analysis in a lab) of affected tissues and/or heart
• Genetic testing for ATTR mutation

Cardiac Amyloidosis Treatment

Treatment of cardiac amyloidosis includes general management of heart failure and arrhythmias, as well as treatments to target the underlying cause.

Heart failure management includes diuretics and dietary salt restriction to treat fluid overload. Some common heart failure medications such as beta-blockers, angiotensin converting enzyme–inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), and aldosterone antagonists are often not tolerated well in people with amyloidosis and do not show the same benefit as in other types of heart failure.

Arrhythmia management may include beta-blockers and antiarrhythmic medications. Pacemaker implantation may be necessary for slow heart rhythms. Cardiologists may also determine whether placement of an implantable cardioverter defibrillator (ICD) is indicated.

In AL amyloidosis, treatment may involve chemotherapy or a stem cell transplant to address the underlying plasma cell disorder. Newer treatments targeting abnormal transthyretin protein in ATTR are being developed. In 2019, the Food and Drug Administration (FDA) approved a medication called tafamidis for treatment of ATTR. This medication works to stabilize transthyretin to prevent further accumulation in the heart.

Complications of Cardiac Amyloidosis

Cardiac amyloidosis has an overall poor prognosis due to the cardiac complications that may arise, including:

• Progression of heart failure
• Dangerous arrhythmias such as atrial fibrillation or ventricular tachycardia
• Heart block
• Sudden cardiac death

If it spreads to other organ systems, it can lead to:

• Kidney failure
• Nerve damage

Treatment Success

Unfortunately, cardiac amyloidosis is often not diagnosed until later stages. However, the understanding of cardiac amyloidosis continues to advance, and new treatments are developing. Treatment success depends on the type of amyloidosis and early diagnosis so that appropriate treatments may be started promptly.

The best chance at successfully managing cardiac amyloidosis is to follow the treatment plan recommended by your healthcare team, which typically will include cardiologists and blood specialists (hematologists). For specific treatments, enrollment in clinical trials may be an option.

Summary

Cardiac amyloidosis is a serious condition caused by misfolded proteins that accumulate in the heart. It can be classified as AL or ATTR based on the type of protein involved. Symptoms can be vague and indistinguishable from other forms of heart failure, but certain clues such as a history of carpal tunnel syndrome, tongue enlargement, and skin findings can increase suspicion.

Diagnosis is through various blood, urine, and imaging tests, though tissue biopsy can confirm diagnosis. Treatment goals include management of heart failure and arrhythmias while targeting the underlying cause. Follow up with a cardiologist is essential for optimal outcomes.