Hereditary Transthyretin (hATTR) Amyloidosis: Effect on Life Expectancy

Hereditary transthyretin (hATTR) amyloidosis is a rare progressive disease that is passed from parent to child. It is caused by a mutant form of the transthyretin (TTR) protein that can damage vital organs in your body.

Because it affects the body tissue and organs you need to survive, hATTR impacts normal life expectancy. Normal TTR brings thyroid hormone and vitamin A to body tissues. The damaged form is more likely to have an odd structure and misfold.

When TTR misfolds, it collects in clusters called amyloid deposits. These clumps can prevent normal function of your heart, nerves, and other body tissue.

The extent to which hATTR affects your life span depends on the type of disease you have and many other factors about your condition. For some people, new treatments can impact the effect of the disease and help improve outcomes.

This article describes hATTR and how it affects your life expectancy. It also describes factors that impact your lifespan and ways to cope with this severe condition.

Life Expectancy Statistics With hATTR Amyloidosis

Life expectancy statistics for hATTR amyloidosis can provide key information about your disease prognosis and treatment options. However, it's important to consider that hATTR amyloidosis is a highly heterogeneous disease. With a wide range of mutations, this disease can affect everyone differently.

Since the clinical presentation and course of hATTR amyloidosis vary widely, data regarding the average life span is also variable. Life expectancy is affected by the organs damaged at baseline and through disease progression in hATTR amyloidosis.

Research indicates that the life expectancy of people with untreated hATTR amyloidosis is between three and 15 years from the onset of symptoms. Survival is poor when the disease is untreated or diagnosis is delayed.

A meta-analysis of 95 studies on the prevalence and all-cause mortality of all types of transthyretin amyloidosis (ATTR) indicates the following:

Survival rates for hATTR amyloidosis at key benchmarks:

• One-year survival rate: 89.4%
• Two-year survival rate: 77.2%
• Five-year survival rate: 52.8%
  
  
• An interaction between survival and hATTR genotypes, with the genotypes known as Val30Met having the lowest mortality and Val122ile/Thr60Ala having the highest mortality
• Higher survival rates at two years (79.9%) and five years (72.4%) for people on drug therapies (tafamidis/patisiran) compared to the survival rate at two years (64%) and five years (45.8%) of those whose disease ran its natural course
  

Factors Influencing hATTR Amyloidosis Life Expectancy

The condition hATTR amyloidosis affects everyone uniquely. Many factors can impact how hATTR amyloidosis affects your life expectancy.

Below are details on factors that may influence your life expectancy.

Disease Impact on Your Heart

The most common cause of death in patients with amyloidosis involves heart complications. As a result, the most significant predictor of life expectancy with hATTR involves the degree to which your heart is affected by amyloid protein deposits.

When amyloid deposits form in your heart, they can make the walls thick and stiff. The result can lead to heart failure. This is a condition in which your heart is unable to pump blood through your body effectively.

Amyloid deposits also interfere with your heart's electrical system and can cause cardiac arrhythmia (an abnormal heart rhythm that beats too fast or slow) and other rhythm disorders.

Type of Gene Mutation Present

Research indicates there are more than 120 mutations known to cause hATTR amyloidosis, some with higher concentrations in certain parts of the world. The specific TTR genetic mutation you inherit from your parents can affect your experience with the disease and how it impacts your life expectancy.

Some variants are more likely to involve cardiomyopathy (heart disease that affects your heart muscle) earlier, a key factor in determining life expectancy.

The most common TTR genetic mutations in the United States include:

• Val1221le: In the United States, this variant is most common in people with West African. About 3.2% of Black Americans have this mutation. This variant is linked with cardiomyopathy and heart failure.
• Val30Met: This variant is the most common worldwide. It is often found in families from Spain, Portugal, France, Sweden, and Japan their descendants. It causes mostly nerve-related symptoms.
• Thr60Ala: This mutation is most common in people of Irish ancestry. It typically damages both your cardiac system and peripheral nervous system (nerves that branch off your spinal cord and extend to all body parts).

Age of Disease Onset

The mutation you inherit affects the age at which symptoms occur. Symptoms can occur as early as 30 years of age, though most types of hATTR amyloidosis begin later in life, typically by age 70. For some people, symptoms may never occur.

Research indicates that having early-onset hATTR amyloidosis may predispose you to less-severe symptoms. People with late-onset (at age 50 or older) hATTR amyloidosis are more likely to have rapid disease progression, a worsening of symptoms, and cardiovascular complications than people with early-onset (younger than age 50) hATTR.

Treatments Used

Treatment type may impact life expectancy.

Liver transplantation: Until the recent approval of drug therapies for hATTR amyloidosis, liver transplantation was the only available treatment. A large international report showed excellent long-term survival rates—including a survival rate of 55.3% at 20 years—among people treated with liver transplantations.

Medical therapies: Since 2018, the Food and Drug Administration (FDA) has approved several therapies for treating hATTR amyloidosis. These novel drugshave proven effective in stabilizing TTR proteins or slowing the liver's production of faulty TTR proteins when administered in the early stages of the disease.

Research indicates these novel therapies can improve quality of life and sometimes increase survival rates. These medications include:

• For evidence of hATTR amyloidosis with neuropathy:
• Wainua (eplontersen)
• Tegesedi (inotersen)
• Onpattro (patisiran)
• Amvuttra (vutrisiran)
• For evidence of hATTR amyloidosis with cardiomyopathy:
• Vyndaquel/Vyndamax (tafamidis)
  

Tips for Coping With Progressive hATTR Amyloidosis

Coping with progressive hATTR involves strategies that impact the physical and emotional toll that this disease can cause. Consider the following tips for managing and copign with a hATTR amyloidosis:

Build a support system: Talk with your family members and others closely involved in your life to help them understand your condition and the type of support you may need in everyday life.

Help your caregivers get the support they need: Help those who help you get the information and support they need as your changing needs affect their lifestyle and emotions.

Manage stress: Dealing with a chronic condition's physical and emotional toll can increase stress. Try the following strategies to reduce stress and avoid its negative impact on your health:

• Talk with loved ones.
• Perform light activity.
• Read for pleasure.
• Participate in hobbies.
• Practice mindfulness meditation and deep breathing.
• Eat a healthy diet to reduce the impact of factors like excess sugar on your mood.
• Maintain healthy sleep habits.

Join a support group: Support groups can be an invaluable resource. Connecting with others with similar experiences can improve your emotional well-being, help you better understand the disease, and learn tips for disease management. Contact the following organizations for information on local and/or online support groups:

• Amyloidosis Foundation
• Amyloidosis Research Consortium
• Amyloidosis Support Groups
  

Summary

With a diagnosis of hATTR amyloidosis, it is normal to wonder about the way this severe disease can affect your life span. While an early diagnosis and treatment can help improve your outcomes, the details can be complex.

Factors such as your exact gene variant and the age of disease onset can impact your outcomes. The wide range of variants means no one common outcome for this disease exists.

With the use of new treatments starting in 2018 and after, many current studies may not reflect the impact of these treatments. Given all these factors, discussing concerns about your mortality with your healthcare provider before making assumptions is key.