Increasing recognition of ATTR cardiac amyloidosis can improve outcomes

Transthyretin Amyloidosis (ATTR) is a multisystemic condition, typically presenting with heart and/or neuropathy symptoms. It is being increasingly recognised in older people due to heightened awareness and advances in cardiac imaging techniques for diagnosis.

Amyloidosis is a general term used to describe a group of diseases where a particular protein ‘misfolds’ and subsequently accumulates into ‘amyloid fibrils’ which get deposited into various tissues and organs, interrupting their normal function and causing progressive disease.

Risk in older people

In ATTR amyloidosis, transthyretin — a normally occurring protein with important roles in the body — misfolds into fibrils as it exits the liver which deposit in the heart and nerves. It is subdivided into two types: genetic (which we call hereditary ATTR) or acquired (which we call wild-type ATTR). Wild-type ATTR typically affects older adults, presenting after the sixth decade of life and most commonly in those above 70 years. Because many of its initial manifestations can overlap with more common cardiac conditions such as high blood pressure, it has historically been underdiagnosed. Hereditary ATTR amyloidosis is caused by a genetic mutation in the TTR gene. While rare, there is a particular variant dominant in Ireland (‘T60A’ or ‘Donegal Amy’). However, over 120 mutations have been described across the world. Effective therapies have recently emerged for both genetic and wild-type subtypes.

Symptoms and signs

The heart and nervous system are the most frequently involved organs. Patients can present with heart failure syndrome or rhythm problems such as irregular heartbeat or slow heartbeat, which can lead to collapse or dizziness. In the nervous system, the ATTR amyloid fibrils can cause numbness and tingling.

Frequently, patients will have a history of carpal tunnel syndrome (trapped nerve-causing pins and needles) in both hands — often many years before their ATTR amyloidosis diagnosis. The ‘autonomic’ nervous system can also be affected. Low blood pressure, diarrhoea or constipation and erectile dysfunction can occur.

How is it diagnosed?

The initial suspicion of ATTR amyloidosis is typically based on an echocardiogram (heart ultrasound) and/or cardiac MRI scan.

A definitive diagnosis can then be made through a non-invasive pathway, using blood tests to outrule any blood cell abnormalities, followed by a special type of bone scan known in short-hand as a ‘DPD scan.’ In more complex cases, a biopsy-led diagnosis may be required.

Dr Ross Murphy Consultant Cardiologist, St James’ Hospital

Gene-silencing drugs are among the innovative treatments for stiff heart

Cardiac amyloidosis is a long-described disorder where a waxy, protein-like substance is deposited on the heart muscle making it stiff and, ultimately, weak.

Cardiac amyloidosis can cause breathlessness (labelled as ‘heart failure’) and heart rhythm problems that can lead to death. It has two main types: one is driven by proteins made by the bone marrow and the other by proteins made in the liver.

Stiff heart syndrome

Both reproduce the same, stiff heart that looks overgrown or too thick on cardiac ultrasound. It can cause neuropathy when protein is deposited in nerves. This leads to tingling in the arms and legs and, sometimes, loss of control on bowel and bladder function.

The bone marrow variety is essentially a type of low-grade cancer requiring chemotherapy to control it. The liver-driven process is often a genetic disorder.

Available treatment

Until the last two years, there was little available treatment, apart from a liver transplant that can sometimes be done if caught early enough.

The liver version (TTR amyloid) can also occur in the elderly even if they don’t have the gene disorder or a family history of it.

Thankfully, there has been a sudden treatment breakthrough using a variety of novel technologies (including ‘gene-silencing’ drugs with possible long-term effects). Two new medications are now licenced in Ireland: a tablet-a-day and another involving intermittent infusion injections.

Helping families

We now have viable treatment to halt the deposition of these proteins. Large-scale clinical studies published years ago suggest that the earlier the patient receives treatment, the better the long-term outcome.

We must find affected families and pick up cases that are still early in development — to increase the amount of genetic testing and offer some hope for a disorder that, for so long, had no treatment.

Don’t live with the pain and discomfort: how to manage ATTR amyloidosis

John Wilson Amyloidosis Patient

It’s important to educate people about ATTR amyloidosis because the symptoms are not always obvious.

I’d never heard of amyloidosis until 2020 — I became unwell at work. I initially thought I was having a heart attack.

In August 2020, I met with my consultant who informed me of the diagnosis. To determine what type I had, I went through several blood tests, and this included genetic testing. We waited up to nearly 10 weeks for the genetic blood results which confirmed I had the hereditary type.

Watch out for symptoms

In November 2020, I was referred to Dr Emer Joyce, a cardiologist with a special interest in amyloidosis. I met with Dr Joyce who confirmed I had amyloidosis which was affecting my heart, joints and nerves. It was at this point we realised that I had symptoms for a lengthy period of time which included severe joint pain in hips, shoulder and feet, reduced feeling from the knees down, tiredness, weight loss and shortness of breath on occasion.

Understanding the symptoms of this condition is important. People may look at me and say “he looks great” when they have no idea that it took me 20 minutes to put my socks on this morning or that I had to stop what I was doing to catch my breath.

Better life with treatment

After several months of information-gathering, doctors visits and cocktails of tablets later, in May 2021, I was told that The National Amyloidosis Centre had advised I may be suitable for a drug trial taking place mid 2021 that involved gene editing. I went over in June for assessments to see whether I was a suitable candidate, and to our disbelief, I was. I went in for review every month, then visits became more spread out. My blood work was improved immensely, and the treatment improved my quality of life. I continue on medication for my heart and the neuropathy (pains). The symptoms vary at times and can be worse or better. I have improved feeling in my legs and feet now, too.

If you are a patient, family member or caregiver and in search of support, you can join the ATTR Amyloidosis All Ireland Support Group on Facebook, visit their website or send them an email, and an advocate will be in contact with you.

Patients’ Support Group

(Facebook) ATTR Amyloidosis

All Ireland Support Group

Website: amy.ie

Email: info@amy.ie