Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

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Synonyms

ATTR-CM, Cardiac amyloidosis, Amyloidosis ATTR, Transthyretin cardiac amyloidosis,

Overview

Transthyretin amyloid cardiomyopathy is a rare but severe cause of restrictive cardiomyopathy, caused by the accumulation of transthyretin fibrils in the myocardium. It can present with new or worsening heart failure or new conduction system disease. Due to the lack of knowledge and efficient diagnostic modalities, this disease was often missed in clinical settings. However, with the advent of contemporary cardiac imaging techniques and effective therapeutic options, early diagnosis and treatment are possible. This activity reviews the pathophysiology, diagnosis, and treatment of Transthyretin amyloid cardiomyopathy and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Symptoms

Symptoms of transthyretin amyloidosis (ATTR-CM) vary depending on the type. People with wild-type ATTR-CM may not have any symptoms. If symptoms occur, they often appear after the age of 65.

Familial ATTR-CM symptoms most commonly occur for the first time in people over 50. However, symptoms can occur as early as your 20s or as late as your 80s.

Symptoms of transthyretin amyloidosis (ATTR-CM) are similar to heart failure symptoms, which include:

  • Shortness of breath (especially when lying down or doing minimal physical activity).
  • Bloated stomach.
  • Confusion or difficulty thinking.
  • Coughing or wheezing (especially when lying down).
  • Edema (fluid retention in your legs, ankles and feet).
  • Arrhythmia (irregular or fast heart rate), especially atrial fibrillation.
  • Heart palpitations.
  • Fatigue.
  • Dizziness or passing out.

Causes

A change to the TTR gene causes familial (hereditary) ATTR-CM. In rare instances, this gene change arises in a person without a family history (a de novo mutation). Black men are more likely to develop familial ATTR-CM.

Experts aren’t sure why some people develop wild-type ATTR-CM. This type most commonly occurs in males over 65, which suggests age and sex may be risk factors.

Regardless of the underlying cause, your body starts to produce faulty TTR proteins. These abnormal proteins break apart, fold up on themselves (misfold) and form clumps of amyloid fibrils. Your blood carries these fibril clumps throughout your body, depositing them in nerves or organs like your heart. Over time, organ or nerve damage occurs.

Prevention

If you have the TTR gene mutation that causes familial ATTR-CM, there’s a 50% chance of passing it to each of your children. Not every child who inherits this gene mutation develops ATTR-CM.

Before having children, you may want to meet with a genetic counselor. This specialist can discuss options like preimplantation genetic diagnosis (PGD). This technique may lower the risk of passing the changed gene to your child. With PGD, healthcare providers select embryos that don’t have the faulty gene. They then implant these embryos into your uterus using in vitro fertilization (IVF).

Diagnosis

Transthyretin amyloidosis (ATTR-CM) can be challenging to diagnose correctly. The familial type can mimic heart (cardiovascular) disease caused by high blood pressure. Some people get an incorrect diagnosis at first.

The wild type doesn’t always cause symptoms. That version of the disease can go undetected until severe problems like heart failure occur.

Tests to diagnose transthyretin amyloidosis include:

  • Electrocardiogram (ECG).
  • Cardiac imaging like echocardiograms, MRIs and positron emission tomography (PET) scans.
  • Bone scan (bone scintigraphy) to check for amyloid deposits.
  • Heart biopsy.
  • Blood tests to look for changes to the TTR gene.

Prognosis

Transthyretin amyloidosis is a progressive disease that eventually causes serious complications. But with newer drugs like tafamidis, and new treatments under development in clinical trials, the outlook is improving. One study showed a 13% increase in the survival rate among people who took tafamidis for 30 months. It’s very important to see a heart doctor regularly to make sure you’re on the appropriate medications to treat your heart.

Treatment

There isn’t a cure for transthyretin amyloidosis (ATTR-CM). And there’s no way to rid the body of existing amyloid deposits. But medications can halt disease progression by slowing or stopping the buildup of protein deposits. You may also receive treatments to ease symptoms caused by other problems like heart failure, arrhythmias and neuropathy.

Certain medications for familial ATTR-CM bind to the TTR protein. These medicines stabilize the condition and stop proteins from misfolding. These drugs include tafamidis (Vyndaqel®, Vyndamax®) and diflunisal (Dolobid®), a nonsteroidal anti-inflammatory drug (NSAID) that providers may use as an off-label treatment. Off-label means the U.S. Food and Drug Administration (FDA) hasn’t approved the drug to treat that specific condition. But the drug is FDA-approved to treat other conditions.

Other medications like inotersen (Tegsedi®) and patisiran (Onpattro®) slow the liver’s production of faulty amyloid proteins.

In rare instances, you may need a:

  • Liver transplant.
  • Kidney transplant.
  • Left ventricular assist device (LVAD) or heart transplant.